Background: Mammography can identify calcifications up to 50–100 μm in size as a surrogate parameter for breast cancer or ductal carcinoma in situ (DCIS). Microcalcifications measuring <50 µm are also associated with breast cancer or DCIS and are frequently not detected on mammography, although they can be detected with dark-field imaging. This study examined whether additional breast examination using X-ray dark-field imaging can increase the detection rate of calcifications. Advances in knowledge: (1) evaluation of additional modality of breast imaging; (2) specific evaluation of breast calcifications. Implications for patient care: the addition of X-ray dark-field imaging to conventional mammography could detect additional calcifications. Methods: Talbot–Lau X-ray phase–contrast imaging and X-ray dark-field imaging were used to acquire images of breast specimens. The radiation dosage with the technique is comparable with conventional mammography. Three X-ray gratings with periods of 5–10 µm between the X-ray tube and the flat-panel detector provide three different images in a single sequence: the conventional attenuation image, differential phase image, and dark-field image. The images were read by radiologists. Radiological findings were marked and examined pathologically. The results were described in a descriptive manner. Results: A total of 81 breast specimens were investigated with the two methods; 199 significant structures were processed pathologically, consisting of 123 benign and 76 malignant lesions (DCIS or invasive breast cancer). X-ray dark-field imaging identified 15 additional histologically confirmed carcinoma lesions that were visible but not declared suspicious on digital mammography alone. Another four malignant lesions that were not visible on mammography were exclusively detected with X-ray dark-field imaging. Conclusions: Adding X-ray dark-field imaging to digital mammography increases the detection rate for breast cancer and DCIS associated lesions with micrometer-sized calcifications. The use of X-ray dark-field imaging may be able to provide more accurate and detailed radiological classification of suspicious breast lesions. Adding X-ray dark-field imaging to mammography may be able to increase the detection rate and improve preoperative planning in deciding between mastectomy or breast-conserving therapy, particularly in patients with invasive lobular breast cancer.

BackgroundX‐ray dark‐field radiography could enhance mammography by providing more information on imaged tissue and microcalcifications. The dark field signal is a measure of small angle scattering and can thus provide additional information on the imaged materials. This information can be useful for material distinction of calcifications and the diagnosis of breast cancer by classifying benign and malign association of these calcifications.Methods:For this study, institutional review board approval was obtained. We present the evaluation of images acquired with interferometric grating‐based x‐ray imaging of 323 microcalcifications (166 malign and 157 benign associated) in freshly dissected breast tissue and compare the results to the information extracted in follow‐up pathological evaluation. The number of imaged calcifications is sufficiently higher than in similar previous studies. Fourteen calcification properties were extracted from the digital images and used as predictors in three different models common in discrimination analysis namely a simple threshold model, a naive Bayes model and a linear regression model, which classify the calcifications as associated with a benign or suspicious finding. Three of these fourteen predictors have been newly defined in this work and are independent from the tissue background surrounding the microcalcifications. Using these predictors no background correction is needed, as in previous works in this field. The new predictors are the length of the first and second principle component of the absorption and dark‐field data, as well as the angle between the first principle component and the dark‐field axis. We called these predictors data length, data width, and data orientation.ResultsIn fourfold cross‐validation malignancy of the imaged tissue was predicted. Models that take only classical absorption predictors into account reached a sensitivity of 53.3% at a specificity of 81.1%. For a combination of predictors that also include dark field information, a sensitivity of 63.2% and specificity of 80.8% were obtained. The included dark field information consisted of the newly introduced parameters, data orientation and data width.ConclusionsWhile remaining at a similar specificity, the sensitivity, with which a trained model was able to distinguish malign from benign associated calcifications, was increased by 10% on including dark‐field information. This suggests grating‐based x‐ray imaging as a promising clinical imaging method in the field of mammography.

X-ray dark-field imaging is a promising technique for lung diagnosis. Due to the alveolar structure of lung tissue, a higher contrast is obtained by the dark-field image compared to the attenuation image. Animal studies indicate an enhancement regarding the detection of lung diseases in early stages. In this publication, we focus on the influence of different Talbot-Lau interferometer specifications while maintaining the x-ray source, sample magnification and detector system. By imaging the same porcine lung with three different grating sets, we analyze the contrast-to-noise ratio of the obtained dark-field images with respect to visibility and correlation length. We demonstrate that relatively large grating periods of the phase and of the analyzer grating are sufficient for high quality lung imaging at reasonable dose levels.

Compared to conventional attenuation x-ray radiographic imaging, the x-ray Talbot-Lau technique provides further information about the scattering and the refractive properties of the object in the beam path. Hence, this additional information should improve the diagnostic process concerning medical applications and non-destructive testing. Nevertheless, until now, due to grating fabrication process, Talbot-Lau imaging suffers from small grating sizes (70 mm diameter). This leads to long acquisition times for imaging large objects. Stitching the gratings is one solution. Another one consists of scanning Talbot-Lau setups. In this publication, we present a compact and very fast scanning setup which enables imaging of large samples. With this setup a maximal scanning velocity of 71.7 mm/s is possible. A resolution of 4.1 lines/mm can be achieved. No complex alignment procedures are necessary while the field of view comprises 17.5 × 150 cm 2 . An improved reconstruction algorithm concerning the scanning approach, which increases robustness with respect to mechanical instabilities, has been developed and is presented. The resolution of the setup in dependence of the scanning velocity is evaluated. The setup imaging qualities are demonstrated using a human knee ex-vivo as an example for a high absorbing human sample.

X-ray phase-contrast imaging is a promising method for medical imaging and non-destructive testing. Information about the attenuation, small-angle scattering and phase-shifting properties of an object can be gained simultaneously in three image modalities using a Talbot–Lau interferometer. This is a highly sensitive approach for retrieving this information. Nevertheless, until now, Talbot–Lau interferometry has been a time-consuming process due to image acquisition by phase-stepping procedures. Thus, methods to accelerate the image acquisition process in Talbot–Lau interferometry would be desirable. This is especially important for medical applications to avoid motion artifacts. In this work, the Talbot–Lau interferometry is combined with the moiré imaging approach. Firstly, the reconstruction algorithm of moiré imaging is improved compared to the standard reconstruction methods in moiré imaging that have been published until now. Thus, blurring artifacts resulting from the reconstruction in the frequency domain can be reduced. Secondly, the improved reconstruction algorithm allows for reducing artifacts in the reconstructed images resulting from inhomogeneities of the moiré pattern in large fields of view. Hence, the feasibility of differential phase-contrast imaging with regard to the integration into workflows in medical imaging and non-destructive testing is improved considerably. New fields of applications can be gained due to the accelerated imaging process—for example, live imaging in medical applications.

X-ray grating-based phase-contrast imaging has raised interest regarding a variety of potential clinical applications, whereas the method is feasible using a medical x-ray tube. Yet, the transition towards a clinical setup remains challenging due to the requirement of mechanical robustness of the interferometer and high demands applying to medical equipment in clinical use. We demonstrate the successful implementation of a Talbot-Lau interferometer in an interventional c-arm setup. The consequence of vibrations induced by the rotating anode of the tube is discussed and the prototype is shown to provide a visibility of 21.4% at a tube voltage of 60 kV despite the vibrations. Regarding clinical application, the prototype is mainly set back due to the limited size of the field of view covering an area of 17 mm × 46 mm. A c-arm offers the possibility to change the optical axis according to the requirements of the medical examination. We provide a method to correct for artifacts that result from the angulation of the c-arm. Finally, the images of a series of measurements with the c-arm in different angulated positions are shown. Thereby, it is sufficient to perform a single reference measurement in parking position that is valid for the complete series despite angulation.

Talbot–Lau x-ray imaging provides additionally to the conventional attenuation image, two further images: the differential phase-contrast image which is especially sensitive to differences in refractive properties and the dark-field image which is showing the x-ray scattering properties of the object. Thus, in the dark-field image sub-pixeled object information can be observed. As it has been shown in recent studies, this is of special interest for lung imaging. Changes in the alveoli structure, which are in the size of one detector pixel, can be seen in the dark-field images. A fast acquisition process is crucial to avoid motion artifacts due to heartbeat and breathing of the patient. Using moiré imaging the images can be acquired with a single-shot exposure. Nevertheless, the spatial resolution is reduced compared to the phase-stepping acquisition. We evaluate the results of both imaging techniques towards their feasibility in clinical routine. Furthermore, we analyse the influence of artificial linear object movement on the image quality, in order to simulate the heartbeat of a patient.

Mammography aims at the detection of early breast cancer and can identify calcifications of up to 50 – 100 µm. However, there is evidence that also microcalcifications of less than 50 µm are associated with breast cancer. These small calcifications are frequently not detected in mammography, whereas this is possible with dark-field imaging. The aim of this study was to prove whether the additional use of dark-field imaging can increase the detection rate of breast cancer.

Grating-based Talbot-Lau x-ray interferometry is a popular method for measuring absorption, phase shift, and small-angle scattering. The standard acquisition method for this modality is phase stepping, where the Talbot pattern is reconstructed from multiple images acquired at different grating positions. We review the implicit assumptions in phase-stepping reconstruction, and find that the assumptions of perfectly known grating positions and homoscedastic noise variance are violated in some scenarios. Additionally, we investigate a recently reported estimation bias in the visibility and dark-field signal. To adapt the phase-stepping reconstruction to these findings, we propose three improvements to the reconstruction. These improvements are (a) to use prior knowledge to compute more accurate grating positions to reduce moiré artifacts, (b) to utilize noise variance information to reduce dark-field and phase noise in high-visibility acquisitions, and (c) to perform correction of an estimation bias in the interferometer visibility, leading to more quantitative dark-field imaging in acquisitions with a low signal-to-noise ratio. We demonstrate the benefit of our methods on simulated data, as well as on images acquired with a Talbot-Lau interferometer.

We report on a radiographic measurement of an ex vivo human knee using a grating-based phase-contrast imaging setup and a medical x-ray tube at a tube voltage of 70 kV. The measurement has been carried out using a Talbot-Lau setup that is suitable to achieve a high visibility in the energy regime of medical imaging.In a medical reading by an experienced trauma surgeon signatures of chondrocalcinosis in the medial meniscus have been identified more evidently using the dark-field image in comparison to the conventional attenuation image. The analysis has been carried out at various dose levels down to 0.14 mGy measured as air kerma, which is a dose comparable to clinically used radiographic devices. The diagnosis has been confirmed by a histological analysis of the meniscus tissue.In the introduced high-frequency filtered phase-contrast image the anterior and posterior horn of the medial meniscus and the posterior cruciate ligament have also been visible.Furthermore, atherosclerotic plaque is visible in both imaging modalities, attenuation and dark-field, despite the presence of overlaying bone.This measurement, for the first time, proves the feasibility of Talbot-Lau x-ray imaging at high-energy spectra above 40 kVp and reasonable dose levels with regard to spacious and dense objects.

In Talbot-Lau x-ray imaging, the fringe visibility provided by the interferometer is a crucial quality parameter to preserve high quality images at an acceptable dose level. The noise of the obtained differential phase signal and the dark-field image is directly influenced by the visibility. To optimize the performance of such an interferometer, we use wave-field simulations to investigate the effect of the phase grating G1. Therefore, we varied the grating parameters duty cycle and grating bar height. Each set of these parameters were evaluated for different propagation distances and for multiple x-ray spectra. In this multidimensional space the interferometer configuration with the highest visibility over a wide range of energies was selected to cover a multiple possible x-ray applications. We manufactured the optimized phase grating G1, the corresponding source grating G0 and analyzer grating G2 and compare the experimental results with the expected results obtained from simulations. The presented measurements show outstanding visibilities up to 50% using a broad x-ray spectrum. These measurements are in very good agreement to the simulation results. The achieved visibility is up to two times higher than for a standard-type setup. This enhancement results in high quality images at a reasonable dose level which we exemplarily demonstrate by imaging a foreign object in a pork trotter.

Purpose Grating‐based Talbot‐Lau interferometers are a popular choice for phase‐contrast X‐ray acquisitions. Here, an air reference scan has to be acquired prior to an object scan. This particularly complicates acquisition of large objects: large objects are tiled into multiple scans due to the small field of view of current gratings. However, phase reference drifts occurring between these scans may require to repeatedly move the object in and out of the X‐ray beam to update the reference information. Methods We developed an image processing technique that completely removes the need for phase reference scans in tiled acquisitions. We estimate the reference from object scans using a tailored iterated robust regression, using a novel efficient optimizer. Results Our evaluation indicates that the estimated reference is not only close to the acquired reference but also improves the final image quality. We hypothesize that this is because we mitigate errors that are introduced when actually acquiring the reference phase. Conclusion Phase‐contrast imaging of larger objects may benefit from computational estimation of phase reference data due to reduced scanning complexity and improved image quality.

X-ray grating-based phase-contrast imaging is a very promising imaging technique for medical imaging and non-destructive testing. Simultaneously to the attenuation properties additional information about the phase-shift and the scattering properties of an object can be gained. Nevertheless, to obtain this information multiple shots per image have to be taken in the so-called phase-stepping process. Thus, it often is a time consuming imaging procedure. In contrast, Moire imaging with a Talbot-Lau interferometer is a very fast single-shot imaging method. To obtain the Moire pattern which encodes the object information the interferometer has to be slightly detuned. This leads to a loss in visibility and therefore to a loss in image quality compared to the more time consuming phase-stepping method. Thus, it is important for the Moire imaging method to evaluate the mechanisms of visibility loss. In this publication we present measurements and simulations investigating the visibility loss due to detuning the Talbot-Lau interferometer. Thus, a deeper understanding of Moire imaging can be gained.

X-ray grating-based phase-contrast Talbot-Lau interferometry is a promising imaging technology that has the potential to raise soft tissue contrast in comparison to conventional attenuation-based imaging. Additionally, it is sensitive to attenuation, refraction and scattering of the radiation and thus provides complementary and otherwise inaccessible information due to the dark-field image, which shows the sub-pixel size granularity of the measured object. Until recent progress the method has been mainly limited to photon energies below 40 keV. Scaling the method to photon energies that are sufficient to pass large and spacious objects represents a challenging task. This is caused by increasing demands regarding the fabrication process of the gratings and the broad spectra that come along with the use of polychromatic X-ray sources operated at high acceleration voltages. We designed a setup that is capable to reach high visibilities in the range from 50 to 120 kV. Therefore, spacious and dense parts of the human body with high attenuation can be measured, such as a human knee. The authors will show investigations on the resulting attenuation, differential phase-contrast and dark-field images. The images experimentally show that X-ray grating-based phase-contrast radiography is feasible with highly absorbing parts of the human body containing massive bones.

PURPOSE X-ray dark-field imaging promises information on the small angle scattering properties even of large samples. However, the dark-field image is correlated with the object's attenuation and phase-shift if a polychromatic x-ray spectrum is used. A method to remove part of these correlations is proposed. METHODS The experimental setup for image acquisition was modeled in a wave-field simulation to quantify the dark-field signals originating solely from a material's attenuation and phase-shift. A calibration matrix was simulated for ICRU46 breast tissue. Using the simulated data, a dark-field image of a human mastectomy sample was corrected for the finger print of attenuation- and phase-image. RESULTS Comparing the simulated, attenuation-based dark-field values to a phantom measurement, a good agreement was found. Applying the proposed method to mammographic dark-field data, a reduction of the dark-field background and anatomical noise was achieved. The contrast between microcalcifications and their surrounding background was increased. CONCLUSIONS The authors show that the influence of and dispersion can be quantified by simulation and, thus, measured image data can be corrected. The simulation allows to determine the corresponding dark-field artifacts for a wide range of setup parameters, like tube-voltage and filtration. The application of the proposed method to mammographic dark-field data shows an increase in contrast compared to the original image, which might simplify a further image-based diagnosis.

Interferometric x-ray imaging becomes more and more attractive for applications such as medical imaging or non-destructive testing, because it provides the opportunity to obtain additional information on the internal structure of radiographed objects.(12) Therefore, three types of images are acquired: An attenuation image like in conventional x-ray imaging, an image of the differential phase-shift generated by the object and the so called dark-field image, which contains information about the object's granularity even on sub-pixel scale.(3)However, most experiments addressing grating-based x-ray phase-contrast imaging with polychromatic sources are restricted to energies up to about 40 keV. For the application of this imaging method to thicker objects like human specimens or dense components, higher tube voltages are required. This is why we designed and constructed a laboratory setup for high energies, which is able to image larger objects.(4)To evaluate the performance of the setup, the mean visibility of the field of view was measured for several tube voltages. The result shows that the mean visibility has a peak value of 23% at a tube voltage of 60 kV and is constantly greater than 16% up to a tube voltage of 120 kV. Thus, good image quality is provided even for high energies. To further substantiate the performance of the setup at high energies, a human ex-vivo foot was examined at a tube voltage of 75 kV. The interferometric x-ray images show a good image quality and a promising diagnostic power.

X-ray grating-based phase-contrast imaging opens new opportunities, inter alia, in medical imaging and non-destructive testing. Because, information about the attenuation properties and about the refractive properties of an object are gained simultaneously.Talbot-Lau imaging requires the knowledge of a reference or free-field image. The long-term stability of a Talbot-Lau interferometer is related to the time span of the validity of a measured reference image. It would be desirable to keep the validity of the reference image for a day or longer to improve feasibility of Talbot-Lau imaging.However, for example thermal and other long-term external influences result in drifting effects of the phase images. Therefore, phases are shifting over time and the reference image is not valid for long-term measurements. Thus, artifacts occur in differential phase-contrast images. We developed an algorithm to determine the differential phase-contrast image with the help of just one calibration image, which is valid for a long time-period. With the help of this algorithm, called phase-plane-fit method, it is possible to save measurement-time, as it is not necessary to take a reference image for each measurement.Additionally, transferring the interferometer technique from laboratory setups to conventional imaging systems the necessary rigidity of the system is difficult to achieve. Therefore, short-term effects like vibrations or distortions of the system lead to imperfections within the phase-stepping procedure. Consequently, artifacts occur in all three image modalities (differential phase-contrast image, attenuation image and dark-field image) of Talbot-Lau imaging. This is a problem with regard to the intended use of phase-contrast imaging for example in clinical routine or non-destructive testing. In this publication an algorithm of Vargas et al is applied and complemented to correct inaccurate phase-step positions with the help of a principal component analysis (PCA). Thus, it is possible to calculate the artifact free images. Subsequently, the whole algorithm is called PCA minimization algorithm.

X-ray grating-based phase-contrast imaging might open up entirely new opportunities in medical imaging. However, transferring the interferometer technique from laboratory setups to conventional imaging systems the necessary rigidity of the system is difficult to achieve. Therefore, vibrations or distortions of the system lead to inaccuracies within the phase-stepping procedure. Given insufficient stability of the phase-step positions, up to now, artifacts in phase-contrast images occur, which lower the image quality. This is a problem with regard to the intended use of phase-contrast imaging in clinical routine as for example tiny structures of the human anatomy cannot be observed.In this contribution we evaluate an algorithm proposed by Vargas et.al.(1) and applied to X-ray imaging by Pelzer et.al.(2) that enables us to reconstruct a differential phase-contrast image without the knowledge of the specific phase-step positions. This method was tested in comparison to the standard reconstruction by Fourier analysis. The quality of phase-contrast images remains stable, even if the phase-step positions are completely unknown and not uniformly distributed. To also achieve attenuation and dark-field images the proposed algorithm has been combined with a further algorithm of Vargas et al.(3) Using this algorithm, the phase-step positions can be reconstructed. With the help of the proper phase-step positions it is possible to get information about the phase, the amplitude and the offset of the measured data.We evaluated this algorithm concerning the measurement of thick objects which show a high absorbency.

To retrieve the phase information of x-rays using a Talbot-Lau interferometer, the knowledge of the grating positions is mandatory. Transferring the interferometer technique from the laboratory to a conventional x-ray imaging system, this requirement is no longer guaranteed. This is due to distortions and vibrations which are coupled into the interferometer. Therefore, we applied a principal-component analysis to Talbot-Lau x-ray phase-contrast data. In experiments we compared this alternative approach for image reconstruction to the conventional procedure. As a result, a superior robustness of the principal-component analysis against imperfect phase-stepping data was found. Furthermore, using the proposed method, the reconstruction of x-ray phase-contrast images from randomly distributed phase-step positions is possible.

The dark-field image obtained in grating-based x-ray phase-contrast imaging can provide information about the objects' microstructures on a scale smaller than the pixel size even with low geometric magnification. In this publication we demonstrate that the dark-field image quality can be enhanced with an energy-resolving pixel detector. Energy-resolved x-ray dark-field images were acquired with a 16-energy-channel photon-counting pixel detector with a 1 mm thick CdTe sensor in a Talbot-Lau x-ray interferometer. A method for contrast-noise-ratio (CNR) enhancement is proposed and validated experimentally. In measurements, a CNR improvement by a factor of 1.14 was obtained. This is equivalent to a possible radiation dose reduction of 23%.