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Background The differentiation of minimal-fat—or low-fat—angiomyolipomas from other renal lesions is clinically challenging in conventional computed tomography. In this work, we have assessed the potential of grating-based x-ray phase-contrast computed tomography (GBPC-CT) for visualization and quantitative differentiation of minimal-fat angiomyolipomas (mfAMLs) and oncocytomas from renal cell carcinomas (RCCs) on ex vivo renal samples. Materials and methods Laboratory GBPC-CT was performed at 40 kVp on 28 ex vivo kidney specimens including five angiomyolipomas with three minimal-fat (mfAMLs) and two high-fat (hfAMLs) subtypes as well as three oncocytomas and 20 RCCs with eight clear cell (ccRCCs), seven papillary (pRCCs) and five chromophobe RCC (chrRCC) subtypes. Quantitative values of conventional Hounsfield units (HU) and phase-contrast Hounsfield units (HUp) were determined and histogram analysis was performed on GBPC-CT and grating-based attenuation-contrast computed tomography (GBAC-CT) slices for each specimen. For comparison, the same specimens were imaged at a 3T magnetic resonance imaging (MRI) scanner. Results We have successfully matched GBPC-CT images with clinical MRI and histology, as GBPC-CT presented with increased soft tissue contrast compared to absorption-based images. GBPC-CT images revealed a qualitative and quantitative difference between mfAML samples (58±4 HUp) and oncocytomas (44±10 HUp, p = 0.057) and RCCs (ccRCCs: 40±12 HUp, p = 0.012; pRCCs: 43±9 HUp, p = 0.017; chrRCCs: 40±7 HUp, p = 0.057) in contrast to corresponding laboratory attenuation-contrast CT and clinical MRI, although not all differences were statistically significant. Due to the heterogeneity and lower signal of oncocytomas, quantitative differentiation of the samples based on HUp or in combination with HUs was not possible. Conclusions GBPC-CT allows quantitative differentiation of minimal-fat angiomyolipomas from pRCCs and ccRCCs in contrast to absorption-based imaging and clinical MRI.

Background To investigate the detection capabilities of myocardial perfusion defects of dual-energy computed tomography (CT) technology using time-resolved iodine-based maps for functional assessment of coronary stenosis in a dynamic heart phantom. Methods An anatomical heart model was designed using a three-dimensional (3D) printing technique. The lumen of the right coronary artery was reduced to 25% of the original areal cross-section. Scans were acquired with a 64-slice dual-layer CT equipment using a perfusion protocol with 36 time points. For distinguishing haemodynamically affected from unaffected myocardial regions, conventional and spectral mean transit time (MTT) parameter maps were compared. A dose reduction technique was simulated by using a subset of time points of the time attenuation curves (TACs). Results The tracer kinetic modeling showed decreased errors on fit parameters from conventional to spectral TACs (42% reduction for A and 40% for λ). Three characteristic regions (highly, moderately, and not affected by the simulated stenosis) can be distinguished in all spectral perfusion maps. The best distinction was observed on MTT maps. An area under the curve (AUC) value of 1.00 for the voxel-wise differentiation of haemodynamically affected tissue was achieved versus a 0.89 AUC for conventional MTT maps. By temporal under-sampling, a dose reduction of approximately 78% from 19 to 4.3 mSv was achieved with a 0.96 AUC. Conclusion Dual-energy CT can provide time-resolved iodine density data, which enables the calculation of absolute quantitative perfusion maps with decreased fitting errors, improving the accuracy for poststenotic myocardial ischaemic detection in a 3D-printed heart phantom.

The separation of mixtures of substances into their individual components plays an important role in many areas of science. In medical imaging, one method is the established analysis using dual-energy computed tomography. However, when analyzing mixtures consisting of more than three individual basis materials, a physical limit is reached that no longer allows this standard analysis. In addition, the X-ray attenuation coefficients of chemically complicated basis materials may not be known and also cannot be determined by other or previous analyses. To address these issues, we developed a novel theoretical approach and algorithm and tested it on samples prepared in the laboratory as well as on ex-vivo medical samples. This method allowed both five-material decomposition and determination or optimization of the X-ray attenuation coefficients of the sample base materials via optimizations of objective functions. After implementation, this new multimodal method was successfully tested on self-mixed samples consisting of the aqueous base solutions iomeprol, eosin Y disodiumsalt, sodium chloride, and pure water. As a first proof of concept of this technique for detailed material decomposition in medicine we analyzed exact percentage composition of ex vivo clots from patients with acute ischemic stroke, using histological analysis as a reference standard.

Gout is the most common form of inflammatory arthritis, caused by the deposition of monosodium urate (MSU) crystals in peripheral joints and tissue. Detection of MSU crystals is essential for definitive diagnosis, however the gold standard is an invasive process which is rarely utilized. In fact, most patients are diagnosed or even misdiagnosed based on manifested clinical signs, as indicated by the unchanged premature mortality among gout patients over the past decade, although effective treatment is now available. An alternative, non-invasive approach for the detection of MSU crystals is X-ray dark-field radiography. In our work, we demonstrate that dark-field X-ray radiography can detect naturally developed gout in animals with high diagnostic sensitivity and specificity based on the in situ measurement of MSU crystals. With the results of this study as a potential basis for further research, we believe that X-ray dark-field radiography has the potential to substantially improve gout diagnostics.

The ability of biomedical imaging data to be of quantitative nature is getting increasingly important with the ongoing developments in data science. In contrast to conventional attenuation-based X-ray imaging, grating-based phase contrast computed tomography (GBPC-CT) is a phase contrast micro-CT imaging technique that can provide high soft tissue contrast at high spatial resolution. While there is a variety of different phase contrast imaging techniques, GBPC-CT can be applied with laboratory X-ray sources and enables quantitative determination of electron density and effective atomic number. In this review article, we present quantitative GBPC-CT with the focus on biomedical applications.

Objectives Dark-field imaging based on small angle X-ray scattering has been shown to be highly sensitive for microcalcifications, e.g. in breast tissue. We hypothesized (i) that high signal areas in dark-field imaging of atherosclerotic plaque are associated with microcalcifications and (ii) that dark-field imaging is more sensitive for microcalcifications than attenuation-based imaging. Methods Fifteen coronary artery specimens were examined at an experimental set-up consisting of X-ray tube (40 kV), grating-interferometer and detector. Tomographic dark-field-, attenuation-, and phase-contrast data were simultaneously acquired. Histopathology served as standard of reference. To explore the potential of dark field imaging in a full-body CT system, simulations were carried out with spherical calcifications of different sizes to simulate small and intermediate microcalcifications. Results Microcalcifications were present in 10/10 (100%) cross-sections with high dark-field signal and without evidence of calcifications in attenuation- or phase contrast. In positive controls with high signal areas in all three modalities, 10/10 (100%) cross-sections showed macrocalcifications. In negative controls without high signal areas, no calcifications were detected. Simulations showed that the microcalcifications generate substantially higher dark-field than attenuation signal. Conclusions Dark-field imaging is highly sensitive for microcalcifications in coronary atherosclerotic plaque and might provide complementary information in the assessment of plaque instability.

Purpose X-ray phase-contrast imaging (PCI) provides additional information beyond absorption characteristics by detecting the phase shift of the X-ray beam passing through material. The grating-based system works with standard polychromatic X-ray sources, promising a possible clinical implementation. PCI has been shown to provide additional information in soft-tissue samples. The aim of this study was to determine if ex vivo quantitative phase-contrast computed tomography (PCCT) may differentiate between pathologic fluid collections. Materials and methods PCCT was performed with the grating interferometry method. A protein serial dilution, human blood samples and 17 clinical samples of pathologic fluid retentions were imaged and correlated with clinical chemistry measurements. Conventional and phase-contrast tomography images were reconstructed. Phase-contrast Hounsfield Units (HUp) were used for quantitative analysis analogously to conventional HU. The imaging was analyzed using overall means, ROI values as well as whole-volume-histograms and vertical gradients. Contrast to noise ratios were calculated between different probes and between imaging methods. Results HUp showed a very good linear correlation with protein concentration in vitro. In clinical samples, HUp correlated rather well with cell count and triglyceride content. PCI was better than absorption imaging at differentiating protein concentrations in the protein samples as well as at differentiating blood plasma from cellular components. PCI also allowed for differentiation of watery samples (such as lymphoceles) from pus. Conclusion Phase-contrast computed tomography is a promising tool for the differentiation of pathologic fluids that appear homogenous with conventional attenuation imaging.

Grating-based x-ray phase-contrast imaging provides three simultaneous image channels originating from a single image acquisition. While the phase signal provides direct access to the electron density in tomography, there is additional information on sub-resolutional structural information which is called dark-field signal in analogy to optical microscopy. The additional availability of the conventional attenuation image qualifies the method for implementation into existing diagnostic routines. The simultaneous access to the attenuation coefficient and the electron density allows for quantitative two-material discrimination as demonstrated lately for measurements at a quasi-monochromatic compact synchrotron source. Here, we investigate the transfer of the method to conventional polychromatic x-ray sources and the additional inclusion of the dark-field signal for three-material decomposition. We evaluate the future potential of grating-based x-ray phase-contrast CT for quantitative three-material discrimination for the specific case of early stroke diagnosis at conventional polychromatic x-ray sources. Compared to conventional CT, the method has the potential to discriminate coagulated blood directly from contrast agent extravasation within a single CT acquisition. Additionally, the dark-field information allows for the clear identification of hydroxyapatite clusters due to their micro-structure despite a similar attenuation as the applied contrast agent. This information on materials with sub-resolutional microstructures is considered to comprise advantages relevant for various pathologies.

Grating-based dark-field interferometry can be realized with lab-based, low-brilliance X-ray sources and provides scattering information of sample structures below the detector pixel size. This unique property allows promising medical imaging applications, especially for lung diseases. Structural damage in lung tissue caused by pulmonary emphysema or pulmonary carcinoma could be observed in radiographs by changes in the dark-field signal with high sensitivity at early stages, in contrast to the conventional absorption signal. Currently, the standard for diagnosis in the clinical routine of pulmonary diseases is absorption computed tomography (CT). The assessment of a larger number of samples with in vivo dark-field CT is limited by the rather long scan times, the order of 2 h, that are required to obtain sufficient CT data quality. In this work, a prototype in vivo, small-animal, dark-field CT is optimized with respect to CT measurements with the following: usage of an iterative reconstruction algorithm for the reduction of undersampling artifacts, a rearranged data acquisition scheme with reduced amount of dead time, and thinned gratings and curved grating geometry for more efficient utilization of the 37 kV X-ray flux. The device performance is evaluated with noise-effective dose measurements, image contrast-to-noise ratio, interferometry visibility across the field-of-view, and a reduced measurement time of 40 min with a deposited dose of 85 mGy.

X-ray phase-contrast imaging is an effective approach to drastically increase the contrast and sensitivity of microtomographic techniques. Numerous approaches to depict the real part of the complex-valued refractive index of a specimen are nowadays available. A comparative study using experimental data from grating-based interferometry and propagation-based phase contrast combined with single-distance phase retrieval applied to a non-homogeneous sample is presented (acquired at beamline ID19-ESRF). It is shown that grating-based interferometry can handle density gradients in a superior manner. The study underlines the complementarity of the two techniques for practical applications.

Grating based X-ray differential phase contrast imaging (DPCI) allows for high contrast imaging of materials with similar absorption characteristics. In the last years' publications, small animals or parts of the human body like breast, hand, joints or blood vessels have been studied. Larger objects could not be investigated due to the restricted field of view limited by the available grating area. In this paper, we report on a new stitching method to increase the grating area significantly: individual gratings are merged on a carrier substrate. Whereas the grating fabrication process is based on the LIGA technology (X-ray lithography and electroplating) different cutting and joining methods have been evaluated. First imaging results using a 2×2 stitched analyzer grating in a Talbot-Lau interferometer have been generated using a conventional polychromatic X-ray source. The image quality and analysis confirm the high potential of the stitching method to increase the field of view considerably.

Phase-contrast computed tomography (PCCT) is an X-ray-based imaging method measuring differences in the refractive index during tissue passage. While conventional X-ray techniques rely on the absorption of radiation due to differing tissue-specific attenuation coefficients, PCCT enables the determination of the electron density (ED). By the analysis of respective phantoms and ex vivo specimens, we identified the components responsible for different electron densities in murine adipose tissue depots to be cellular fat and mitochondrial content, two parameters typically different between white adipose tissue (WAT) and brown adipose tissue (BAT). Brown adipocytes provide mammals with a means of non-shivering thermogenesis to defend normothermia in a cold environment. Brown adipocytes are found in dedicated BAT depots and interspersed within white fat depots, a cell type referred to as brite (brown in white) adipocyte. Localization and quantification of brown and brite adipocytes in situ allows an estimate of depot thermogenic capacity and potential contribution to maximal metabolic rate in the cold. We utilized PCCT to infer the composition of white, brite, and brown adipose tissue from ED of individual depots. As proof of principle, we imaged mice 10, 20, and 30 days of age. During this period, several WAT depots are known to undergo transient browning. Based on ED, classical WAT and BAT could be clearly distinguished. Retroperitoneal and inguinal WAT depots increased transiently in ED during the known remodeling from white to brite/brown and back to white. We systematically analyzed 18 anatomically defined adipose tissue locations and identified changes in fat content and mitochondrial density that imply an orchestrated pattern of simultaneous browning and whitening on the organismic level. Taken together, PCCT provides a three-dimensional imaging technique to visualize ED of tissues in situ. Within the adipose organ, ED provides a measure of mitochondrial density and fat content. Depending on experimental setting, these constitute surrogate markers of cellular distribution of white, brite, and brown adipocytes and thereby an estimate of thermogenic capacity.

Phase-contrast computed tomography (PCCT) is an X-ray-based imaging method measuring differences in the refractive index during tissue passage. While conventional X-ray techniques rely on the absorption of radiation due to differing tissue-specific attenuation coefficients, PCCT enables the determination of the electron density (ED). By the analysis of respective phantoms and ex vivo specimens, we identified the components responsible for different electron densities in murine adipose tissue depots to be cellular fat and mitochondrial content, two parameters typically different between white adipose tissue (WAT) and brown adipose tissue (BAT). Brown adipocytes provide mammals with a means of non-shivering thermogenesis to defend normothermia in a cold environment. Brown adipocytes are found in dedicated BAT depots and interspersed within white fat depots, a cell type referred to as brite (brown in white) adipocyte. Localization and quantification of brown and brite adipocytes in situ allows an estimate of depot thermogenic capacity and potential contribution to maximal metabolic rate in the cold. We utilized PCCT to infer the composition of white, brite, and brown adipose tissue from ED of individual depots. As proof of principle, we imaged mice 10, 20, and 30 days of age. During this period, several WAT depots are known to undergo transient browning. Based on ED, classical WAT and BAT could be clearly distinguished. Retroperitoneal and inguinal WAT depots increased transiently in ED during the known remodeling from white to brite/brown and back to white. We systematically analyzed 18 anatomically defined adipose tissue locations and identified changes in fat content and mitochondrial density that imply an orchestrated pattern of simultaneous browning and whitening on the organismic level. Taken together, PCCT provides a three-dimensional imaging technique to visualize ED of tissues in situ. Within the adipose organ, ED provides a measure of mitochondrial density and fat content. Depending on experimental setting, these constitute surrogate markers of cellular distribution of white, brite, and brown adipocytes and thereby an estimate of thermogenic capacity.

Grating-based X-ray phase-contrast (gbPC) is an X-ray phase-contrast imaging method involving optical gratings that typically employs the Talbot self-imaging effect. X-ray phase contrast is known to provide significant benefits for biomedical imaging. To investigate these benefits for gbPC, a high-sensitivity gbPC micro-CT setup for small biological samples has been constructed. A gbPC projection measurement simultaneously retrieves the transmittance, differential-phase and dark-field modalities of a sample. Phase stepping, the most common gbPC acquisition technique, involves several acquisitions at different lateral positions of one of the gratings. The three modalities can then be retrieved by least-squares- or FFT-based methods. Unfortunately, increasing differential-phase sensitivity also leads to an increased magnitude of artifacts introduced during retrieval of the modalities from the phase-stepping data, which limits image quality. Most importantly, processing of phase-stepping data with incorrect stepping positions (i.e., spatial sampling jitter) can introduce artifacts to the modalities. Using data from the high-sensitivity gbPC setup, as well as simulations, we show that an artifact is introduced by the jitter which is correlated with the phase of the stepping curve. We present a theoretical explanation for this correlation by introducing small deviations to an equidistant sampling of a stepping curve and approximating the effect on the calculation of the three gbPC modalities with a first-order Taylor approximation. Finally, we present an algorithm for the detection and removal of these artifacts that exploits these correlations. We show that this algorithm is able to eliminate these artifacts without degrading true image information.

The demand for quantitative medical imaging is increasing in the ongoing digitalization. Conventional computed tomography (CT) is energy-dependent and therefore of limited comparability. In contrast, dual-energy CT (DECT) allows for the determination of absolute image contrast quantities, namely the electron density and the effective atomic number, and is already established in clinical radiology and radiation therapy. Grating-based phase-contrast computed tomography (GBPC-CT) is an experimental X-ray technique that also allows for the measurement of the electron density and the effective atomic number. However, the determination of both quantities is challenging when dealing with polychromatic GBPC-CT setups. In this paper, we present how to calculate the effective atomic numbers with a polychromatic, laboratory GBPC-CT setup operating between 35 and 50\,kVp. First, we investigated the accuracy of the measurement of the attenuation coefficients and electron densities. For this, we performed a calibration using the concept of effective energy. With the reliable experimental quantitative values, we were able to evaluate the effective atomic numbers of the investigated materials using a method previously shown with monochromatic X-ray radiation. In detail, we first calculated the ratio of the electron density and attenuation coefficient, which were experimentally determined with our polychromatic GBPC-CT setup. Second, we compared this ratio with tabulated total attenuation cross sections from literature values to determine the effective atomic numbers. Thus, we were able to calculate two physical absolute quantities -- the electron density and effective atomic number -- that are in general independent of the specific experimental conditions like the X-ray beam spectrum or the setup design.

Objectives: Grating-based phase-contrast computed tomography (gb-PCCT) relies on x-ray refraction instead of absorption to generate high-contrast images in biological soft tissue. The aim of this study was to evaluate the potential of gb-PCCT for the depiction of structural changes in heart disease.& para;& para;Materials and Methods: Four human heart specimens from patients with hypertensive disease, ischemic disease, dilated heart disease, and cardiac lipomatosis were examined. The gb-PCCT setup consisted of an x-ray tube (40 kV, 70 mA), grating-interferometer, and detector, and allowed simultaneous aquisition of phase- and absorption-contrast data. With histopathology as the standard of reference, myocardium (MC), fibrotic scar (FS), interstitial fibrosis (IF), and fatty tissue (FT) were visually and quantitatively evaluated. Systematic differences in absorption- and phase-contrast Hounsfield units (HUabs and HUp) were assessed. & para;& para;Results: Thirteen corresponding cross-sections were included, and MC, FS, IF, and FT were found in 13 (100%), 4 (30.8%), 7 (53.8%), and 13 (100%) cross-sections, respectively. Mean HUp/HUabs, were 52.5/54.1, 86.6/69.7, 62.4/62.3, and -38.6/-258.9 for MC, FS, IF, and FT, respectively. An overlap in HU(abs )was observed for MC and IF (P = 0.84) but not for HUp (P < 0.01). Contrast-to-noise ratios were significantly higher in phase- than in absorption-contrast or MC/FT (35.4 vs 7.8;P < 0.01) and for MC/FS (12.3 vs 0.2;P < 0.01).& para;& para;Conclusions: Given its superior soft tissue contrast, gb-PCCT is able to depict structural changes in different cardiomyopathies, which can currently not be obtained by x-ray absorption-based imaging methods. If current technical limitations can be overcome, gb-PCCT may evolve as a powerful tool for the anatomical assessment of cardiomyopathy.

The conventional form of computed tomography using X-ray attenuation without any contrast agents is of limited use for the characterization of soft tissue in many fields of medical and biological studies. Grating-based phase-contrast computed tomography (gbPC-CT) is a promising alternative imaging method solving the low soft tissue contrast without the need of any contrast agent. While highly sensitive measurements are possible using conventional X-ray sources the spatial resolution does often not fulfill the requirements for specific imaging tasks, such as visualization of pathologies. The focus of this study is the increase in spatial resolution without loss of sensitivity. To overcome this limitation a super-resolution reconstruction based on sub-pixel shifts involving a deconvolution of the image data during each iteration is applied. In our study we achieve an effective pixel size of 28 μm with a conventional rotating anode tube and a photon-counting detector. We also demonstrate that the method can upgrade existing setups to measure tomographies with higher resolution. The results show the increase in resolution at high sensitivity and with the ability to make quantitative measurements. The combination of sparse sampling and statistical iterative reconstruction may be used to reduce the total measurement time. In conclusion, we present high-quality and high-resolution tomographic images of biological samples to demonstrate the experimental feasibility of super-resolution reconstruction.

Background Currently, the detection of retained wood is a frequent but challenging task in emergency care. The purpose of this study is to demonstrate improved foreign-body detection with the novel approach of preclinical X-ray dark-field radiography. Methods At a preclinical dark-field x-ray radiography, setup resolution and sensitivity for simultaneous detection of wooden and metallic particles have been evaluated in a phantom study. A clinical setting has been simulated with a formalin fixated human hand where different typical foreign-body materials have been inserted. Signal-to-noise ratios (SNR) have been determined for all test objects. Results On the phantom, the SNR value for wood in the dark-field channel was strongly improved by a factor 6 compared to conventional radiography and even compared to the SNR of an aluminium structure of the same size in conventional radiography. Splinters of wood

The distant goal of this investigation is to reduce the number of invasive procedures associated with breast micro calcification biopsies, by improving and refining conventional BIRADS micro calcification assessments with x-ray dark-field mammography. The study was institutional review board (IRB) approved. A dedicated grating-based radiography setup (Mo-target, 40 keV, 70 mA) was used to investigate one breast mastectomy and 31 biopsies with dark-field mammography. Comparing the absorption and scattering properties of micro calcifications clusters enables accessing information on the interior morphology on the micron-scale retrieved in a non-invasive manner. Insights underlying the micro morphological nature of breast calcifications were verified by comprehensive high-resolution micro-CT measurements. It was found that Dark-field mammography allows a micro-structural classification of breast micro calcification as ultra-fine, fine, pleomorphic and coarse textured using conventional detectors. Dark-field mammography is thereby highly sensitive to minor structural deviations. Finally, the determined micro-texture of the investigated micro calcifications was correlated with findings obtained from histopathological work up. The presented results demonstrate that dark-field mammography yields the potential to enhance diagnostic validity of current micro calcification analysis - which is yet limited to the exterior appearance of micro calcification clusters - and thereby reduce the number of invasive procedures.

Grating-based phase-contrast computed tomography (gbPC-CT) is a promising imaging method for imaging of soft tissue contrast without the need of any contrast agent. The focus of this study is the increase in spatial resolution without loss in sensitivity to allow visualization of pathologies comparable to the convincing results obtained at the synchrotron. To improve the effective pixel size a super-resolution reconstruction based on subpixel shifts involving a deconvolution of the image is applied on differential phase-contrast data. In our study we could achieve an effective pixel sizes of 28mm without any drawback in terms of sensitivity or the ability to measure quantitative data.

Grating-based X-ray phase-contrast (gbPC) is known to provide significant benefits for biomedical imaging. To investigate these benefits, a high-sensitivity gbPC micro-CT setup for small (≈ 5 cm) biological samples has been constructed. Unfortunately, high differential-phase sensitivity leads to an increased magnitude of data processing artifacts, limiting the quality of tomographic reconstructions. Most importantly, processing of phase-stepping data with incorrect stepping positions can introduce artifacts resembling Moire fringes to the projections. Additionally, the focal spot size of the X-ray source limits resolution of tomograms. Here we present a set of algorithms to minimize artifacts, increase resolution and improve visual impression of projections and tomograms from the examined setup. We assessed two algorithms for artifact reduction: Firstly, a correction algorithm exploiting correlations of the artifacts and differential-phase data was developed and tested. Artifacts were reliably removed without compromising image data. Secondly, we implemented a new algorithm for flatfield selection, which was shown to exclude flat-fields with strong artifacts. Both procedures successfully improved image quality of projections and tomograms. Deconvolution of all projections of a CT scan can minimize blurring introduced by the finite size of the X-ray source focal spot. Application of the Richardson-Lucy deconvolution algorithm to gbPC-CT projections resulted in an improved resolution of phase-contrast tomograms. Additionally, we found that nearest-neighbor interpolation of projections can improve the visual impression of very small features in phase-contrast tomograms. In conclusion, we achieved an increase in image resolution and quality for the investigated setup, which may lead to an improved detection of very small sample features, thereby maximizing the setup's utility.

Current clinical imaging methods face limitations in the detection and correct characterization of different subtypes of renal cell carcinoma (RCC), while these are important for therapy and prognosis. The present study evaluates the potential of grating-based X-ray phase-contrast computed tomography (gbPC-CT) for visualization and characterization of human RCC subtypes. The imaging results for 23 ex vivo formalin-fixed human kidney specimens obtained with phase-contrast CT were compared to the results of the absorption-based CT (gbCT), clinical CT and a 3T MRI and validated using histology. Regions of interest were placed on each specimen for quantitative evaluation. Qualitative and quantitative gbPC-CT imaging could significantly discriminate between normal kidney cortex (54 ± 4 HUp) and clear cell (42 ± 10), papillary (43 ± 6) and chromophobe RCCs (39 ± 7), p

Breast microcalcifications play an essential role in the detection and evaluation of early breast cancer in clinical diagnostics. However, in digital mammography, microcalcifications are merely graded with respect to their global appearance within the mammogram, while their interior microstructure remains spatially unresolved and therefore not considered in cancer risk stratification. In this article, we exploit the sub-pixel resolution sensitivity of X-ray dark-field contrast for clinical microcalcification assessment. We demonstrate that the micromorphology, rather than chemical composition of microcalcification clusters (as hypothesised by recent literature), determines their absorption and small-angle scattering characteristics. We show that a quantitative classification of the inherent microstructure as ultra-fine, fine, pleomorphic and coarse textured is possible. Insights underlying the micromorphological nature of breast calcifications are verified by comprehensive high-resolution micro-CT measurements. We test the determined microtexture of microcalcifications as an indicator for malignancy and demonstrate its potential to improve breast cancer diagnosis, by providing a non-invasive tool for sub-resolution microcalcification assessment. Our results indicate that dark-field imaging of microcalcifications may enhance the diagnostic validity of current microcalcification analysis and reduce the number of invasive procedures.

Differential phase-contrast X-ray imaging using a Talbot-Lau interferometer has recently shown promising results for applications in medical imaging. However, reducing the applied radiation dose remains a major challenge. In this study, we consider the realization of a Talbot-Lau interferometer in a high Talbot order to increase the signal-to-noise ratio for low-dose applications. The quantitative performance of π and π/2 systems at high Talbot orders is analyzed through simulations, and the design energy and X-ray spectrum are optimized for mammography. It is found that operation even at very high Talbot orders is feasible and beneficial for image quality. As long as the X-ray spectrum is matched to the visibility spectrum, the SNR continuously increases with the Talbot order for π-systems. We find that the optimal X-ray spectra and design energies are almost independent of the Talbot order and that the overall imaging performance is robust against small variations in these parameters. Discontinuous spectra, such as that from molybdenum, are less robust because the characteristic lines may coincide with minima in the visibility spectra; however, they may offer slightly better performance. We verify this hypothesis by realizing a prototype system with a mean fringe visibility of above 40% at the seventh Talbot order. With this prototype, a proof-of-principle measurement of a freshly dissected breast at reasonable compression to 4 cm is conducted with a mean glandular dose of only 3 mGy but with a high SNR.

Grating based X-ray phase contrast imaging is on the verge of being applied in clinical settings. To achieve this goal, compact setups with high sensitivity and dose efficiency are necessary. Both can be increased by eliminating unwanted absorption in the beam path, which is mainly due to the grating substrates. Fabrication of gratings via deep X-ray lithography can address this issue by replacing the commonly used silicon substrate with materials with lower X-ray absorption that fulfill certain boundary conditions. Gratings were produced on both graphite and polymer substrates without compromising on structure quality. These gratings were tested in a three-grating setup with a source operated at 40 kVp and lead to an increase in the detector photon count rate of almost a factor of 4 compared to a set of gratings on silicon substrates. As the visibility was hardly affected, this corresponds to a significant increase in sensitivity and therefore dose efficiency.

Correspondence: Quantitative evaluation of X-ray dark-field images for microcalcification analysis in mammography

The purpose of this work is to develop an image-based de-noising algorithm that exploits complementary information and noise statistics from multi-modal images, as they emerge in x-ray tomography techniques, for instance grating-based phase-contrast CT and spectral CT. Among the noise reduction methods, image-based de-noising is one popular approach and the so-called bilateral filter is a well known algorithm for edge-preserving filtering. We developed a generalization of the bilateral filter for the case where the imaging system provides two or more perfectly aligned images. The proposed generalization is statistically motivated and takes the full second order noise statistics of these images into account. In particular, it includes a noise correlation between the images and spatial noise correlation within the same image. The novel generalized three-dimensional bilateral filter is applied to the attenuation and phase images created with filtered backprojection reconstructions from grating-based phase-contrast tomography. In comparison to established bilateral filters, we obtain improved noise reduction and at the same time a better preservation of edges in the images on the examples of a simulated soft-tissue phantom, a human cerebellum and a human artery sample. The applied full noise covariance is determined via cross-correlation of the image noise. The filter results yield an improved feature recovery based on enhanced noise suppression and edge preservation as shown here on the example of attenuation and phase images captured with grating-based phase-contrast computed tomography. This is supported by quantitative image analysis. Without being bound to phase-contrast imaging, this generalized filter is applicable to any kind of noise-afflicted image data with or without noise correlation. Therefore, it can be utilized in various imaging applications and fields.

Phase-contrast mammography using laboratory X-ray sources is a promising approach to overcome the relatively low sensitivity and specificity of clinical, absorption-based screening. Current research is mostly centered on identifying potential diagnostic benefits arising from phase-contrast and dark-field mammography and benchmarking the latter with conventional state-of-the-art imaging methods. So far, little effort has been made to adjust this novel imaging technique to clinical needs. In this article, we address the key points for a successful implementation to a clinical routine in the near future and present the very first dose-compatible and rapid scan-time phase-contrast mammograms of both a freshly dissected, cancer-bearing mastectomy specimen and a mammographic accreditation phantom.

Phase-contrast x-ray computed tomography (PCCT) is currently investigated and developed as a potentially very interesting extension of conventional CT, because it promises to provide high soft-tissue contrast for weakly absorbing samples. For data acquisition several images at different grating positions are combined to obtain a phase-contrast projection. For short exposure times, which are necessary for lower radiation dose, the photon counts in a single stepping position are very low. In this case, the currently used phase-retrieval does not provide reliable results for some pixels. This uncertainty results in statistical phase wrapping, which leads to a higher standard deviation in the phase-contrast projections than theoretically expected. For even lower statistics, the phase retrieval breaks down completely and the phase information is lost. New measurement procedures rely on a linear approximation of the sinusoidal phase stepping curve around the zero crossings. In this case only two images are acquired to obtain the phase-contrast projection. The approximation is only valid for small phase values. However, typically nearly all pixels are within this regime due to the differential nature of the signal. We examine the statistical properties of a linear approximation method and illustrate by simulation and experiment that the lower statistical limit can be redefined using this method. That means that the phase signal can be retrieved even with very low photon counts and statistical phase wrapping can be avoided. This is an important step towards enhanced image quality in PCCT with very low photon counts.

To evaluate the potential of grating-based phase-contrast computed-tomography (gb-PCCT) to classify human carotid and coronary atherosclerotic plaques according to modified American Heart Association (AHA) criteria. Experiments were carried out at a laboratory-based set-up consisting of X-ray tube (40 kVp), grating-interferometer and detector. Eighteen human carotid and coronary artery specimens were examined. Histopathology served as the standard of reference. Vessel cross-sections were classified as AHA lesion type I/II, III, IV/V, VI, VII or VIII plaques by two independent reviewers blinded to histopathology. Conservative measurements of diagnostic accuracies for the detection and differentiation of plaque types were evaluated. A total of 127 corresponding gb-PCCT/histopathology sections were analyzed. Based on histopathology, lesion type I/II was present in 12 (9.5 %), III in 18 (14.2 %), IV/V in 38 (29.9 %), VI in 16 (12.6 %), VII in 34 (26.8 %) and VIII in 9 (7.0 %) cross-sections. Sensitivity, specificity and positive and negative predictive value were ≥0.88 for most analyzed plaque types with a good level of agreement (Cohen’s kappa = 0.90). Overall, results were better in carotid (kappa = 0.97) than in coronary arteries (kappa = 0.85). Inter-observer agreement was high with kappa = 0.85, p

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.

Grating-based x-ray differential phase-contrast imaging (DPCI) is capable of acquiring information based on phase-shift and dark-field signal, in addition to conventional x-ray absorption-contrast. Thus DPCI gives an advantage to investigate composite materials with component wise similar absorption properties like soft tissues. Due to technological challenges in fabricating high quality gratings over a large extent, the field of view (FoV) of the imaging systems is limited to a grating area of a couple of square centimeters. For many imaging applications (e.g. in medicine), however, a FoV that ranges over several ten centimeters is needed. In this manuscript we propose to create large area gratings of theoretically any extent by assembling a number of individual grating tiles. We discuss the precision needed for alignment of each microstructure tile in order to reduce image artifacts and to preserve minimum 90% of the sensitivity obtainable with a monolithic grating. To achieve a reliable high precision alignment a semiautomatic assembly system consisting of a laser autocollimator, a digital microscope and a force sensor together with positioning devices was built. The setup was used to tile a first four times four analyzer grating with a size of 200 mm × 200 mm together with a two times two phase grating. First imaging results prove the applicability and quality of the tiling concept.

Objectives Conventional X-ray attenuation-based contrast is inherently low for the soft-tissue components of the female breast. To overcome this limitation, we investigate the diagnostic merits arising from dark-field mammography by means of certain tumour structures enclosed within freshly dissected mastectomy samples. Methods We performed grating-based absorption, absolute phase and dark-field mammography of three freshly dissected mastectomy samples containing bi- and multifocal carcinoma using a compact, laboratory Talbot-Lau interferometer. Preoperative in vivo imaging (digital mammography, ultrasound, MRI), postoperative histopathological analysis and ex vivo digital mammograms of all samples were acquired for the diagnostic verification of our results. Results In the diagnosis of multifocal tumour growth, dark-field mammography seems superior to standard breast imaging modalities, providing a better resolution of small, calcified tumour nodules, demarcation of tumour boundaries with desmoplastic stromal response and spiculated soft-tissue strands extending from an invasive ductal breast cancer. Conclusions On the basis of selected cases, we demonstrate that dark-field mammography is capable of outperforming conventional mammographic imaging of tumour features in both calcified and non-calcified tumours. Presuming dose optimization, our results encourage further studies on larger patient cohorts to identify those patients that will benefit the most from this promising additional imaging modality. Key Points • X-ray dark-field mammography provides significantly improved visualization of tumour features • X-ray dark-field mammography is capable of outperforming conventional mammographic imaging • X-ray dark-field mammography provides imaging sensitivity towards highly dispersed calcium grains

Background: Fibroadenoma is the most common benign solid breast lesion type and a very common cause for histologic assessment. To justify a conservative therapy, a highly specific discrimination between fibroadenomas and other breast lesions is crucial. Phase-contrast imaging offers improved soft-tissue contrast and differentiability of fine structures combined with the potential of 3-dimensional imaging. In this study we assessed the potential of grating-based phase-contrast CT imaging for visualizing diagnostically relevant features of fibroadenomas. Materials and Methods: Grating-based phase-contrast CT was performed on six ex-vivo formalin-fixed breast specimens containing a fibroadenoma and three samples containing benign changes that resemble fibroadenomas using Talbot Lau interferometry and a polychromatic X-ray source. Phase-contrast and simultaneously acquired absorption-based 3D-datasets were manually matched with corresponding histological slices. The visibility of diagnostically valuable features was assessed in comparison with histology as the gold-standard. Results: In all cases, matching of grating-based phase-contrast CT images and histology was successfully completed. Grating-based phase-contrast CT showed greatly improved differentiation of fine structures and provided accurate depiction of strands of fibrous tissue within the fibroadenomas as well as of the diagnostically valuable dilated, branched ductuli of the fibroadenomas. A clear demarcation of tumor boundaries in all cases was provided by phase- but not absorption-contrast CT. Conclusions: Pending successful translation of the technology to a clinical setting and considerable reduction of the required dose, the data presented here suggest that grating-based phase- contrast CT may be used as a supplementary non-invasive diagnostic tool in breast diagnostics. Phase-contrast CT may thus contribute to the reduction of false positive findings and reduce the recall and core biopsy rate in population-based screening. Phase-contrast CT may further be used to assist during histopathological workup, offering a 3D view of the tumor and helping to identify diagnostically valuable tissue sections within large tumors.

Phase-contrast x-ray imaging is a promising improvement of conventional absorption-based mammography for early tumor detection. This potential has been demonstrated recently, utilizing structured gratings to obtain differential phase and dark-field scattering images. However, the inherently anisotropic imaging sensitivity of the proposed mono-directional approach yields only insufficient diagnostic information, and has low diagnostic sensitivity to highly oriented structures. To overcome these limitations, we present a two-directional x-ray phase-contrast mammography approach and demonstrate its advantages by applying it to a freshly dissected, cancerous mastectomy breast specimen. We illustrate that the two-directional scanning procedure overcomes the insufficient diagnostic value of a single scan, and reliably detects tumor structures, independently from their orientation within the breast. Our results indicate the indispensable diagnostic necessity and benefit of a multi-directional approach for x-ray phase-contrast mammography.

In this article, we report on a novel acquisition scheme for time- and dose-saving retrieval of dark-field data in grating-based phase-contrast imaging. In comparison to currently available techniques, the proposed approach only requires two phase steps. More importantly, our method is capable of accurately retrieving the dark-field signal where conventional approaches fail, for instance in the case of very low photon statistics. Finally, we successfully extend two-shot dark-field imaging to tomographic investigations, by implementing an iterative reconstruction with appropriate weights. Our results indicate an important progression towards the clinical feasibility of dark-field tomography.