X-ray Phase-contrast CT Research Articles

Multiscale X-ray phase-contrast CT uncovers adaptive changes and compensatory mechanisms of circulatory pathways during acute liver injury

Intrahepatic circulation is essential for the repair of acute liver injury (ALI); however, very limited information is available concerning changes in the circulatory pathways during ALI. Therefore, multi-scale X-ray phase-contrast CT combined with three-dimensional (3D) visualization is used to quantitatively analyze the intrahepatic circulation pathway (including the hepatic vein, portal vein and hepatic sinusoid) in the mouse model via the intraperitoneal injection of carbon tetrachloride (CCl4) from acute injury to recovery. The results demonstrate that the liver still preserves some vessel-like channels accessed to the central vein when the injury causes the severe collapse of the hepatic sinusoids that cannot be observed in two-dimensional pathologic slices. Moreover, angiogenesis is observed in the terminal branches of the hepatic vein and portal vein. Additionally, we extend the two-dimensional primary lobule to a 3D model and find that the sinusoids in zone III have the most severe injury. The sinusoids in different zones also show changes in parameters such as density and mean diameter during the ALI. In conclusion, phase-contrast CT can reveal the intact vascular system within the liver lobes, thus providing critical information for studying the mechanisms involved in the evolution of circulatory structures from damage to repair.

Multiscale X-ray phase-contrast CT unveils the evolution of bile infarct in obstructive biliary disease

Bile infarct is a pivotal characteristic of obstructive biliary disease, but its evolution during the disease progression remains unclear. Our objective, therefore, is to explore morphological alterations of the bile infarct in the disease course by means of multiscale X-ray phase-contrast CT. Bile duct ligation is performed in mice to mimic the obstructive biliary disease. Intact liver lobes of the mice are scanned by phase-contrast CT at various resolution scales. Phase-contrast CT clearly presents three-dimensional (3D) images of the bile infarcts down to the submicron level with good correlation with histological images. The CT data illustrates that the infarct first appears on day 1 post-BDL, while a microchannel between the infarct and hepatic sinusoids is identified, the number of which increases with the disease progression. A 3D model of hepatic acinus is proposed, in which the infarct starts around the portal veins (zone I) and gradually progresses towards the central veins (zone III) during the disease process. Multiscale phase-contrast CT offers the comprehensive analysis of the evolutionary features of the bile infarct in obstructive biliary disease. During the course of the disease, the bile infarcts develop infarct-sinusoidal microchannels and gradually occupy the whole liver, promoting the disease progression.

Obliteration of portal venules contributes to portal hypertension in biliary cirrhosis.

The effects of the obliteration of portal venules (OPV) in cirrhotic portal hypertension are poorly understood. To investigate its contribution to portal hypertension in biliary cirrhosis and its underlying mechanism,we evaluated OPV using two-dimensional (2D) histopathology in liver explants from patients with biliary atresia (BA, n = 63), primary biliary cholangitis (PBC, n = 18), and hepatitis B-related cirrhosis (Hep-B-cirrhosis, n = 35). Then, three-dimensional (3D) OPV was measured by X-ray phase-contrast CT in two parallel models in rats following bile duct ligation (BDL) or carbon tetrachloride (CCl4) administration, representing biliary cirrhosis and post-necrotic cirrhosis, respectively. The portal pressure was also measured in the two models. Finally, the effects of proliferative bile ducts on OPV were investigated. We found that OPV was significantly more frequent in patients with biliary cirrhosis, including BA (78.57 ± 16.45%) and PBC (60.00 ± 17.15%), than that in Hep-B-cirrhotic patients (29.43 ± 14.94%, p < 0.001). OPV occurred earlier, evidenced by the paired liver biopsy at a Kasai procedure (KP), and was irreversible even after a successful KP in the patients with BA. OPV was also significantly more frequent in the BDL models than in the CCl4 models, as shown by 2D and 3D quantitative analysis. Portal pressure was significantly higher in the BDL model than that in the CCl4 model. With the proliferation of bile ducts, portal venules were compressed and irreversibly occluded, contributing to the earlier and higher portal pressure in biliary cirrhosis. OPV, as a pre-sinusoidal component, plays a key role in the pathogenesis of portal hypertension in biliary cirrhosis. The proliferated bile ducts and ductules gradually take up the 'territory' originally attributed to portal venules and compress the portal venules, which may lead to OPV in biliary cirrhosis. © 2024 The Pathological Society of Great Britain and Ireland.

Retracted: Study on the Cytotoxic Microstructure of Titanium Dioxide Nanoparticles by X-Ray Phase-Contrast CT Imaging.

[This retracts the article DOI: 10.1155/2022/2413922.].

Towards virtual histology with X-ray grating interferometry

Breast cancer is the most common type of cancer worldwide. Diagnosing breast cancer relies on clinical examination, imaging and biopsy. A core-needle biopsy enables a morphological and biochemical characterization of the cancer and is considered the gold standard for breast cancer diagnosis. A histopathological examination uses high-resolution microscopes with outstanding contrast in the 2D plane, but the spatial resolution in the third, Z-direction, is reduced. In the present paper, we propose two high-resolution table-top systems for phase-contrast X-ray tomography of soft-tissue samples. The first system implements a classical Talbot–Lau interferometer and allows to perform ex-vivo imaging of human breast samples with a voxel size of 5.57 μm. The second system with a comparable voxel size relies on a Sigray MAAST X-ray source with structured anode. For the first time, we demonstrate the applicability of the latter to perform X-ray imaging of human breast specimens with ductal carcinoma in-situ. We assessed image quality of both setups and compared it to histology. We showed that both setups made it possible to target internal features of breast specimens with better resolution and contrast than previously achieved, demonstrating that grating-based phase-contrast X-ray CT could be a complementary tool for clinical histopathology.

Human lung virtual histology by multi-scale x-ray phase-contrast computed tomography

Objectives. As the central organ of the respiratory system, the human lung is responsible for supplying oxygen to the blood, which reaches the erythrocytes by diffusion through the alveolar walls and is then distributed throughout the body. By exploiting the difference in electron density detected by a phase shift in soft tissue, high-resolution x-ray phase-contrast computed tomography (XPCT) can resolve biological structures in a sub-μm range, shedding new light on the three-dimensional structure of the lungs, physiological functions and pathological mechanisms. Approach. This work presents both synchrotron and laboratory XPCT results of postmortem tissue from autopsies and biopsies embedded with various preparation protocols such as precision-cut lung slices, cryogenically fixed lung tissue, as well as paraffin and alcohol fixed tissue. The selection of pathological abnormalities includes channel of Lambert, bronchus-associated lymphoid tissue and alveolar capillary dysplasia with misalignment of pulmonary veins. Subsequently, quantification and visualization approaches are presented. Main results. The overall high image quality even of in-house XPCT scans for the case of FFPE biopsies can be exploited for a wide range of pulmonary pathologies and translated to dedicated and optimized instrumentation which could be operated in clinical setting. By using synchrotron radiation, contrast can be further increased to resolve sub-μm sized features down to the sub-cellular level. The results demonstrate that a wide range of preparation protocols including sample mounting in liquids can be used. Significance. With XPCT, poorly understood 3D structures can be identified in larger volume overview and subsequently studied in more detail at higher resolution. With the full 3D structure, the respective physiological functions of airways or vascular networks, and the different pathophysiologic mechanisms can be elucidated or at least underpinned with structural data. Moreover, synchrotron data can be used to validate laboratory protocols and provide ground truth for standardizing the method.

Insight into microvascular adaptive alterations in the Glisson system of biliary atresia after Kasai portoenterostomy using X-ray phase-contrast CT.

To investigate microvascular alterations in the Glisson system of biliary atresia (BA) patients after Kasai portoenterostomy (KP) using three-dimensional (3D) virtual histopathology based on X-ray phase-contrast CT (PCCT). Liver explants from BA patients were imaged using PCCT, and 32 subjects were included and divided into two groups: KP (n = 16) and non-KP (n = 16). Combined with histological analysis and 3D visualization technology, 3D virtual histopathological assessment of the biliary, arterial, and portal venous systems was performed. According to loop volume ratio, 3D spatial density, relative surface area, tortuosity, and other parameters, pathological changes of microvasculature in the Glisson system were investigated. In the non-KP group, bile ducts mostly manifested as radial multifurcated hyperplasia and twisted into loops. In the KP group, the bile duct hyperplasia was less, and the loop volume ratio of bile ducts decreased by 13.89%. Simultaneously, the arterial and portal venous systems presented adaptive alterations in response to degrees of bile duct hyperplasia. Compared with the non-KP group, the 3D spatial density of arteries in the KP group decreased by 3.53%, and the relative surface area decreased from 0.088 ± 0.035 to 0.039 ± 0.015 (p < .01). Deformed portal branches gradually recovered after KP, with a 2.93% increase in 3D spatial density and a decrease in tortuosity from 1.17 ± 0.06 to 1.14 ± 0.04 (p < .01) compared to the non-KP group. 3D virtual histopathology via PCCT clearly reveals the microvascular structures in the Glisson system of BA patients and provides key insights into the morphological mechanism of microvascular adaptation induced by biliary tract dredging after KP in BA disease. • 3D virtual histopathology via X-ray phase-contrast computed tomography clearly presented the morphological structures and pathological changes of microvasculature in the Glisson system of biliary atresia patients. • The morphological alterations of microvasculature in the Glisson system followed the competitive occupancy mechanism in the process of biliary atresia.

Quantifying lung aeration in neonatal lambs at birth using lung ultrasound.

BackgroundLung ultrasound (LUS) is a safe and non-invasive tool that can potentially assess regional lung aeration in newborn infants and reduce the need for X-ray imaging. LUS produces images with characteristic artifacts caused by the presence of air in the lung, but it is unknown if LUS can accurately detect changes in lung air volumes after birth. This study compared LUS images with lung volume measurements from high-resolution computed tomography (CT) scans to determine if LUS can accurately provide relative measures of lung aeration.MethodsDeceased near-term newborn lambs (139 days gestation, term ∼148 days) were intubated and the chest imaged using LUS (bilaterally) and phase contrast x-ray CT scans at increasing static airway pressures (0–50 cmH2O). CT scans were analyzed to calculate regional air volumes and correlated with measures from LUS images. These measures included (i) LUS grade; (ii) brightness (mean and coefficient of variation); and (iii) area under the Fourier power spectra within defined frequency ranges.ResultsAll LUS image analysis techniques correlated strongly with air volumes measured by CT (p < 0.01). When imaging statistics were combined in a multivariate linear regression model, LUS predicted the proportion of air in the underlying lung with moderate accuracy (95% prediction interval ± 22.15%, r2 = 0.71).ConclusionLUS can provide relative measures of lung aeration after birth in neonatal lambs. Future studies are needed to determine if LUS can also provide a simple means to assess air volumes and individualize aeration strategies for critically ill newborns in real time.

Iterative phase contrast CT reconstruction with novel tomographic operator and data-driven prior.

Breast cancer remains the most prevalent malignancy in women in many countries around the world, thus calling for better imaging technologies to improve screening and diagnosis. Grating interferometry (GI)-based phase contrast X-ray CT is a promising technique which could make the transition to clinical practice and improve breast cancer diagnosis by combining the high three-dimensional resolution of conventional CT with higher soft-tissue contrast. Unfortunately though, obtaining high-quality images is challenging. Grating fabrication defects and photon starvation lead to high noise amplitudes in the measured data. Moreover, the highly ill-conditioned differential nature of the GI-CT forward operator renders the inversion from corrupted data even more cumbersome. In this paper, we propose a novel regularized iterative reconstruction algorithm with an improved tomographic operator and a powerful data-driven regularizer to tackle this challenging inverse problem. Our algorithm combines the L-BFGS optimization scheme with a data-driven prior parameterized by a deep neural network. Importantly, we propose a novel regularization strategy to ensure that the trained network is non-expansive, which is critical for the convergence and stability analysis we provide. We empirically show that the proposed method achieves high quality images, both on simulated data as well as on real measurements.

Observation of processed rice using synchrotron radiation X-ray phase-contrast imaging.

As a result of increasing elderly population, the number of people with dysphagia and difficulty eating is expected to increase as well. It is not always feasible to cook meals to the proper texture for elderly individuals and people with dysphagia living at home. Accordingly, there is high market demand for ready-made texture-modified foods for home consumption. Many methods have been widely used to analyze the structural properties of foods. However, it is difficult to observe the structure of foods in a nondestructive manner with the conventional analysis methods. To observe food as it is without destroying it, we adopted X-ray phase-contrast computed tomography (CT) using a crystal interferometer in this study. The samples were commercially available precooked rice porridge and two texture-modified rice products satisfying the Universal Design Food criteria. A texture profile analysis was also performed to compare the phase-contrast images and the food properties. In the phase-contrast images, both the ingredients and cohesion in the samples were successfully observed. It was also found that the texture-modified rice products were easier to eat and swallow than the rice porridge. These results show that X-ray phase-contrast CT using a crystal interferometer is a promising method for nondestructive observation of food structures and is expected to open up new horizons in food science.

The first 3D analysis of the sphenoid morphogenesis during the human embryonic period

The sphenoid has a complicated shape, and its morphogenesis during early development remains unknown. We aimed to elucidate the detailed morphogenesis of the sphenoid and to visualize it three-dimensionally using histological section (HS) and phase-contrast X-ray CT (PCX-CT). We examined 65 specimens using HS and 57 specimens using PCX-CT, and summarized the initial morphogenesis of the sphenoid during Carnegie stage (CS) 17 to 23. The 3D models reconstructed using PCX-CT demonstrated that some neural foramina have the common process of "neuro-advanced" formation and revealed that shape change in the anterior sphenoid lasts longer than that of the posterior sphenoid, implying that the anterior sphenoid may have plasticity to produce morphological variations in the human face. Moreover, we measured the cranial base angle (CBA) in an accurate midsagittal section acquired using PCX-CT and found that the CBA against CS was largest at CS21. Meanwhile, CBA against body length showed no striking peak, suggesting that the angulation during the embryonic period may be related to any developmental events along the progress of stages rather than to a simple body enlargement. Our study elucidated the normal growth of the embryonic sphenoid, which has implications for the development and evolution of the human cranium.

High-Resolution X-ray Phase-Contrast Imaging and Sensory and Rheometer Tests in Cooked Edamame.

Although several reports exist on the use of X-ray analysis in vegetables and fruits to examine internal disorders, cavities, and porosity, information on X-ray analysis of qualities, such as texture, is lacking as well as information on X-ray analysis of legumes. Therefore, this study aimed to perform X-ray analysis with sensory and rheometer tests in cooked vegetable soybean (edamame). Edamame is popular worldwide due to its deliciousness and nutritional value. Vascular structures and cracks around them were clearly visualized using X-ray phase-contrast computed tomography (CT) imaging. In addition, we observed the fine structure of the seed coat, which could be important for seed development, germination, and processing. The density in the edamame beans declined as the boiling time increased, promoting a reduction in hardness described in sensory and rheometer tests. The reduction in density proceeded from the gap between cotyledons, the opposite side of the hypocotyl, and the crack. Collectively, the findings show that the high-resolution X-ray phase-contrast CT imaging conducted in a nondestructive manner may help in effectively evaluating the quality of vegetables and in observing the internal structures related to plant development.

A method of three-dimensional branching geometry to differentiate the intrahepatic vascular type in early-stage liver fibrosis using X-ray phase-contrast CT

PurposeDifferentiating the intrahepatic vascular type is essential for the early diagnosis of liver fibrosis. X-ray phase-contrast computed tomography (PCCT) is a label-free, high-resolution imaging modality for imaging vascular networks in a whole liver lobe. This study explores the use of three-dimensional (3D) branching geometry to differentiate between the hepatic vein (HV) and portal vein (PV) in early-stage liver fibrosis with PCCT. MethodBile duct ligation surgery was conducted in mice to induce early-stage liver fibrosis. The individual liver lobes of mice were imaged using PCCT, and morphological characteristics, including vascular diameter, cross-sectional area, eccentricity, branch angle, bifurcation index, area ratio and junction exponent, were investigated in 3D modality. These characteristics were used to differentiate the HV from the PV, and their performance was evaluated through receiver operating characteristic (ROC) curve analysis. ResultsPCCT revealed a 3D vascular structure of the liver lobes. For intact lobes, the differentiation method between the HV and PV using the junction exponent had an AUC of 0.99 (95% CI: 0.98–1.00). Moreover, the AUCs of the junction exponent for 15, 10, and 5 branches in dissected lobes for differentiation were 0.98 (95% CI: 0.94–1.00), 0.86 (95% CI: 0.73–0.99) and 0.82 (95% CI: 0.67–0.97), respectively. ConclusionThe method of 3D branching geometry using the junction exponent could differentiate the HV from PV in early-stage liver fibrosis via the PCCT, which provides the foundation for further analysis of liver fibrosis.

Study on the Cytotoxic Microstructure of Titanium Dioxide Nanoparticles by X-Ray Phase-Contrast CT Imaging.

To address the problem of microstructural analysis of titania nanoparticles with high cytotoxicity, the authors propose X-ray phase-comparative CT imaging studies. In this method, the HE-stained section samples were compared with the X-ray phase-contrast CT imaging microscopic images, and 3D texture analysis was used to observe the changes in the preparation of hepatocyte microstructures in the two groups. The results show that X-ray phase-contrast CT imaging microscopic images and their larger image size are closely related to HE staining images, and X-ray phase-contrast CT microscopic images can observe important data of hepatocytes from multiple angles. The ship skeleton extraction method based on the endpoint limit also has advantages over traditional algorithms in extraction accuracy and can provide more 3D feature files, confirming the growth and transformation of normal hepatocytes into hepatocyte cytotoxic microstructures. The distribution effect of using the ensemble process is better than the simple 2D feature set and 3D feature set, and the overall accuracy is improved; the result distribution of the tree determination and random forest methods is also better than that of the support vector machine method. The experimental results show that the X-ray phase-contrast CT images can highlight the 2D and 3D imaging features of the hepatotoxic microstructure of TiO2 nanoparticles and provide data for quantitative analysis.

In-situ deformation imaging of articular cartilage using grating-based phase-contrast X-ray CT at a synchrotron light source

Quantification of deformation behavior of articular cartilage (AC) is crucial for understanding its mechanical function and response to mechanical stimuli. Here, we explored whether grating-based phase-contrast X-ray CT using monochromatic synchrotron light (grating-based msPXCT) enables in-situ quantification of local deformation in AC. Grating-based msPXCT of a porcine AC sample during axial compression test was conducted using a Talbot grating interferometer. Local displacements and strains were computed using a digital volume correlation method. The magnitude of axial strain decreased from the upper to middle sample zones and reached almost constant over the middle-lower zone, consistent with the depth-dependent density increase with compression. Thus, grating-based msPXCT may be suitable for quantitative analysis of AC deformation.

Ring artifact removal for differential phase-contrast X-ray computed tomography using a conditional generative adversarial network.

The integration process used as a pre-processing step in the reconstruction of differential phase-contrast X-ray CT (d-PCCT) causes the measurement noise to propagate throughout the projection image, which is leading to increased ring artifacts (RA) in the reconstructed image. It is difficult to eliminate the RA using conventional RA removal methods that were developed for the absorption-based CT field. We propose an effective method that can remove RA of d-PCCT images. The proposed method uses Laplacian images reconstructed from second-derivative projections of d-PCCT. This method is based on a conditional generative adversarial network (cGAN), whose loss function is designed by adding the L1- and L2-norm to the original cGAN. The training data were taken from a numerical phantom generated by a d-PCCT imaging simulator. To validate the applicability of the trained network, we tested its RA removal effect on test data from numerical phantoms generated randomly and actual experimental data. The results of numerical validation using numerical phantoms showed that the proposed method improved the RA removal effect compared to conventional methods. In addition, image comparison by visual evaluation showed that only the proposed method was able to remove RA while preserving original structures in the actual biological d-PCCT images. We proposed a cGAN-based method for RA removal that exploits the physical properties of d-PCCT. The proposed method was able to completely remove RA from d-PCCT images on both simulated data and biological data. We believe that this method is useful for the observation of various types of biological soft tissue.

Sparse-domain regularized stripe decomposition combined with guided-image filtering for ring artifact removal in propagation-based x-ray phase-contrast CT

Propagation-based x-ray phase-contrast computed tomography (PB-PCCT) images often suffer from severe ring artifacts. Ring artifacts are mainly caused by the nonuniform response of detector elements, and they can degrade image quality and affect the subsequent image processing and quantitative analyses. To remove ring artifacts in PB-PCCT images, a novel method combined sparse-domain regularized stripe decomposition (SDRSD) method with guided image filtering (GIF) was proposed. In this method, polar coordinate transformation was utilized to convert the ring artifacts to stripe artifacts. And then considering the directional and sparse properties of the stripe artifacts and the continuity characteristics of the sample, the SDRSD method was designed to remove stripe artifacts. However, for the SDRSD method, the presence of noise may destroy the edges of the stripe artifacts and lead to incomplete decomposition. Hence, a simple and efficient smoothing technique, namely GIF, was employed to overcome this issue. The simulations and real experiments demonstrated that the proposed method could effectively remove ring artifacts as well as preserve the structures and edges of the samples. In conclusion, the proposed method can serve as an effective tool to remove ring artifacts in PB-PCCT images, and it has high potential for promoting the biomedical and preclinical applications of PB-PCCT.

Insight into Bile Duct Reaction to Obstruction from a Three-dimensional Perspective Using ex Vivo Phase-Contrast CT.

Background Biliary obstruction leads to an increase in biliary pressure within the biliary system, which induces the morphologic adaptation of the biliary tree. Purpose To observe and to quantify the morphologic characteristics of the adaptation in a bile duct ligation rat model and verify it in patients with biliary atresia in a three-dimensional (3D) manner using x-ray phase-contrast CT. Materials and Methods A bile duct ligation model was induced in 40 male Sprague-Dawley rats, which were divided into five groups: the control group (no ligation) and groups 2, 4, 6, and 8 weeks after bile duct ligation (eight animals in each group). Liver tissue samples (approximately 1.8 cm in length and 1.3 cm in height) were imaged by using phase-contrast CT and compared with histologic analysis. With a combination of phase-contrast CT and 3D visualization technology, the entire biliary system and the intrahepatic vascular system were quantitatively analyzed according to downstream, midstream, and upstream domains based on bile duct volume, surface area, and other parameters. Additionally, liver explant tissues from 28 patients with biliary atresia were studied to determine the impact of biliary tract reconstruction. Results To offset the increased biliary pressure within the biliary system, the ductular reaction in the downstream, midstream, and upstream domains manifested as dilatation, spiderweb-like looping, and interconnected honeycomb-like patterns, respectively. The most severe ductular reaction occurred in the upstream domain, and the relative surface area (mean, 0.02 μm-1 ± 0.01, 0.04 μm-1 ± 0.01, 0.07 μm-1 ± 0.02, and 0.10 μm-1 ± 0.02 for the 2-8-week groups, respectively; P < .01 among the groups) and volume fraction of ductules (mean, 16.54% ± 4.62, 19.69% ± 6.41, 26.92% ± 5.82, and 38.34% ± 10.36 for the 2-8-week groups, respectively; P < .01 among the groups except between the 2- and 4-week groups [P = .062]) significantly increased over time. In patients with biliary atresia, it was observed that both fibrosis and proliferative ductules regressed after successful biliary tract reconstruction following Kasai portoenterostomy. Furthermore, ductular reaction was accompanied by a progressive increase in the arterial supply but a loss of portal blood supply. Conclusion X-ray phase-contrast CT with three-dimensional rendering of the biliary system in a bile duct ligation rat model provides key insights into ductular reaction or biliary self-adaptation triggered by increased biliary pressure. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Vannier and Wang in this issue.

Observation of Morphology in Conductive Rubber Using High-resolution Phase-contrast X-ray CT

Observation of Morphology in Conductive Rubber Using High-resolution Phase-contrast X-ray CT

Single spectrum three-material decomposition with grating-based x-ray phase-contrast CT

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.