Search

Abstract Background Dark-field radiography imaging exploits the wave character of x-rays to measure small-angle scattering on material interfaces, providing structural information with low radiation exposure. We explored the potential of dark-field imaging of bone microstructure to improve the assessment of bone strength in osteoporosis. Methods We prospectively examined 14 osteoporotic/osteopenic and 21 non-osteoporotic/osteopenic human cadaveric vertebrae (L2–L4) with a clinical dark-field radiography system, micro-computed tomography (CT), and spectral CT. Dark-field images were obtained in both vertical and horizontal sample positions. Bone microstructural parameters (trabecular number, Tb.N; trabecular thickness, Tb.Th; bone volume fraction, BV/TV; degree of anisotropy, DA) were measured using standard ex vivo micro-CT, while hydroxyapatite density was measured using spectral CT. Correlations were assessed using Spearman rank correlation coefficients. Results The measured dark-field signal was lower in osteoporotic/osteopenic vertebrae (vertical position, 0.23 ± 0.05 versus 0.29 ± 0.04, p

Abstract The introduction of mammography screening programs has significantly reduced breast cancer mortality rates. Nevertheless, some lesions remain undetected, especially in dense breast tissue. Studies have shown that phase-contrast imaging can improve breast cancer diagnosis by increasing soft tissue contrast. Furthermore, grating-based phase-contrast imaging enables the simultaneous acquisition of absorption, phase-contrast, and scattering, so-called dark-field images. The latter allows the classification of microcalcifications. In addition, breast computed tomography (BCT) systems can identify and discriminate overlapping but clinically relevant structures. This study investigates the benefit of combining grating-based phase-contrast with BCT. We explore the potential of grating-based phase-contrast breast computed tomography (gbpc-BCT) with a breast phantom and a freshly dissected fibroadenoma. Improved image contrast could be achieved with radiation doses comparable to those used in clinical BCT.

Abstract Background Chondrosarcomas are rare malignant bone tumors diagnosed by analyzing radiological images and histology of tissue biopsies and evaluating features such as matrix calcification, cortical destruction, trabecular penetration, and tumor cell entrapment. Methods We retrospectively analyzed 16 cartilaginous tumor tissue samples from three patients (51-, 54-, and 70-year-old) diagnosed with a dedifferentiated chondrosarcoma at the femur, a moderately differentiated chondrosarcoma in the pelvis, and a predominantly moderately differentiated chondrosarcoma at the scapula, respectively. We combined a hematein-based x-ray staining with high-resolution three-dimensional (3D) microscopic x-ray computed tomography (micro-CT) for nondestructive 3D tumor assessment and tumor margin evaluation. Results We detected trabecular entrapment on 3D micro-CT images and followed bone destruction throughout the volume. In addition to staining cell nuclei, hematein-based staining also improved the visualization of the tumor matrix, allowing for the distinction between the tumor and the bone marrow cavity. The hematein-based staining did not interfere with further conventional histology. There was a 5.97 ± 7.17% difference between the relative tumor area measured using micro-CT and histopathology (p = 0.806) (Pearson correlation coefficient r = 0.92, p = 0.009). Signal intensity in the tumor matrix (4.85 ± 2.94) was significantly higher in the stained samples compared to the unstained counterparts (1.92 ± 0.11, p = 0.002). Conclusions Using nondestructive 3D micro-CT, the simultaneous visualization of radiological and histopathological features is feasible. Relevance statement 3D micro-CT data supports modern radiological and histopathological investigations of human bone tumor specimens. It has the potential for being an integrative part of clinical preoperative diagnostics. Key points • Matrix calcifications are a relevant diagnostic feature of bone tumors. • Micro-CT detects all clinically diagnostic relevant features of x-ray-stained chondrosarcoma. • Micro-CT has the potential to be an integrative part of clinical diagnostics. Graphical Abstract

Abstract Background We aimed to improve the image quality (IQ) of sparse-view computed tomography (CT) images using a U-Net for lung metastasis detection and determine the best tradeoff between number of views, IQ, and diagnostic confidence. Methods CT images from 41 subjects aged 62.8 ± 10.6 years (mean ± standard deviation, 23 men), 34 with lung metastasis, 7 healthy, were retrospectively selected (2016–2018) and forward projected onto 2,048-view sinograms. Six corresponding sparse-view CT data subsets at varying levels of undersampling were reconstructed from sinograms using filtered backprojection with 16, 32, 64, 128, 256, and 512 views. A dual-frame U-Net was trained and evaluated for each subsampling level on 8,658 images from 22 diseased subjects. A representative image per scan was selected from 19 subjects (12 diseased, 7 healthy) for a single-blinded multireader study. These slices, for all levels of subsampling, with and without U-Net postprocessing, were presented to three readers. IQ and diagnostic confidence were ranked using predefined scales. Subjective nodule segmentation was evaluated using sensitivity and Dice similarity coefficient (DSC); clustered Wilcoxon signed-rank test was used. Results The 64-projection sparse-view images resulted in 0.89 sensitivity and 0.81 DSC, while their counterparts, postprocessed with the U-Net, had improved metrics (0.94 sensitivity and 0.85 DSC) (p = 0.400). Fewer views led to insufficient IQ for diagnosis. For increased views, no substantial discrepancies were noted between sparse-view and postprocessed images. Conclusions Projection views can be reduced from 2,048 to 64 while maintaining IQ and the confidence of the radiologists on a satisfactory level. Relevance statement Our reader study demonstrates the benefit of U-Net postprocessing for regular CT screenings of patients with lung metastasis to increase the IQ and diagnostic confidence while reducing the dose. Key points • Sparse-projection-view streak artifacts reduce the quality and usability of sparse-view CT images. • U-Net-based postprocessing removes sparse-view artifacts while maintaining diagnostically accurate IQ. • Postprocessed sparse-view CTs drastically increase radiologists’ confidence in diagnosing lung metastasis. Graphical Abstract

Abstract Background Nowadays, there is no method to quantitatively characterize the material composition of acute ischemic stroke thrombi prior to intervention, but dual-energy CT (DE-CT) offers imaging-based multimaterial decomposition. We retrospectively investigated the material composition of thrombi ex vivo using DE-CT with histological analysis as a reference. Methods Clots of 70 patients with acute ischemic stroke were extracted by mechanical thrombectomy and scanned ex vivo in formalin-filled tubes with DE-CT. Multimaterial decomposition in the three components, i.e., red blood cells (RBC), white blood cells (WBC), and fibrin/platelets (F/P), was performed and compared to histology (hematoxylin/eosin staining) as reference. Attenuation and effective Z values were assessed, and histological composition was compared to stroke etiology according to the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria. Results Histological and imaging analysis showed the following correlation coefficients for RBC (r = 0.527, p

Abstract Background To determine whether denoised areal bone mineral density (BMD) measurements from scout scans in spectral detector computed tomography (CT) correlate with volumetric trabecular BMD for opportunistic osteoporosis screening. Methods A 64-slice single-source dual-layer spectral CT scanner was used to acquire scout scan data of 228 lumbar vertebral bodies within 57 patients. Scout scans in anterior–posterior (AP) view were performed with a dose of

Frank, Gassert et al. use dark-field chest X-ray imaging to assess COVID-19-pneumonia. Dark-field imaging has a higher sensitivity for COVID-19-pneumonia than attenuation-based imaging and provides an ultralow dose alternative to computed tomography imaging for that purpose.

Abstract 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.

Abstract 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.

Background: Dark-field imaging is a novel imaging modality that allows for the assessment of material interfaces by exploiting the wave character of x-ray. While it has been extensively studied in chest imaging, only little is known about the modality for imaging other tissues. Therefore, the purpose of this study was to evaluate whether a clinical X-ray dark-field scanner prototype allows for the assessment of osteoporosis.Materials and methods: In this prospective study we examined human cadaveric lumbar spine specimens (vertebral segments L2 to L4). We used a clinical prototype for dark-field radiography that yields both attenuation and dark-field images. All specimens were scanned in lateral orientation in vertical and horizontal position. All specimens were additionally imaged with CT as reference. Bone mineral density (BMD) values were derived from asynchronously calibrated quantitative CT measurements. Correlations between attenuation signal, dark-field signal and BMD were assessed using Spearman’s rank correlation coefficients. The capability of the dark-field signal for the detection of osteoporosis/osteopenia was evaluated with receiver operating characteristics (ROC) curve analysis.Results: A total of 58 vertebrae from 20 human cadaveric spine specimens (mean age, 73 years ±13 [standard deviation]; 11 women) were studied. The dark-field signal was positively correlated with the BMD, both in vertical (r = 0.56, p < .001) and horizontal position (r = 0.43, p < .001). Also, the dark-field signal ratio was positively correlated with BMD (r = 0.30, p = .02). No correlation was found between the signal ratio of attenuation signal and BMD (r = 0.14, p = .29). For the differentiation between specimens with and without osteoporosis/osteopenia, the area under the ROC curve (AUC) was 0.80 for the dark-field signal in vertical position.Conclusion: Dark-field imaging allows for the differentiation between spine specimens with and without osteoporosis/osteopenia and may therefore be a potential biomarker for bone stability.

Abstract Background Spirometry and conventional chest x-ray have limitations in investigating early emphysema, while computed tomography, the reference imaging method in this context, is not part of routine patient care due to its higher radiation dose. In this work, we investigated a novel low-dose imaging modality, dark-field chest x-ray, for the evaluation of emphysema in patients with alpha1-antitrypsin deficiency. Methods By exploiting wave properties of x-rays for contrast formation, dark-field chest x-ray visualises the structural integrity of the alveoli, represented by a high signal over the lungs in the dark-field image. We investigated four patients with alpha1-antitrypsin deficiency with a novel dark-field x-ray prototype and simultaneous conventional chest x-ray. The extent of pulmonary function impairment was assessed by pulmonary function measurement and regional emphysema distribution was compared with CT in one patient. Results We show that dark-field chest x-ray visualises the extent of pulmonary emphysema displaying severity and regional differences. Areas with low dark-field signal correlate with emphysematous changes detected by computed tomography using a threshold of -950 Hounsfield units. The airway parameters obtained by whole-body plethysmography and single breath diffusing capacity of the lungs for carbon monoxide demonstrated typical changes of advanced emphysema. Conclusions Dark-field chest x-ray directly visualised the severity and regional distribution of pulmonary emphysema compared to conventional chest x-ray in patients with alpha1-antitrypsin deficiency. Due to the ultra-low radiation dose in comparison to computed tomography, dark-field chest x-ray could be beneficial for long-term follow-up in these patients.

Abstract Grating-based X-ray imaging employs high aspect ratio absorption gratings to generate contrast induced by attenuating, phase-shifting, and small-angle scattering properties of the imaged object. The fabrication of the absorption gratings remains a crucial challenge of the method on its pathway to clinical applications. We explore a simple and fast centrifugal tungsten particle deposition process into silicon-etched grating templates, which has decisive advantages over conventional methods. For that, we use a bimodal tungsten particle suspension which is introduced into a custom designed grating holder and centrifuged at over 1000×g. Gratings with 45 µm period, 450 µm depth, and 170 mm × 38 mm active area are successfully processed reaching a homogeneous absorber filling. The effective absorbing tungsten thickness in the trenches is 207 µm resulting in a filling ratio of 46.6% compared to a voidless filling. The grating was tested in a Talbot–Lau interferometer designed for clinical X-ray dark-field computed tomography, where visibilities up to 33.6% at 60 kV were achieved.

Direct ink writing as additive manufacturing technique was used to print two different boehmite based shapes, cylinders and monoliths, serving as catalyst carriers. These were wet impregnated targeting 0.3–0.9 wt% platinum loadings. ICP-OES, μCT and microscopy revealed dependencies from calcination temperature, geometry and platinum loading. Dehydrogenation reactions of perhydro dibenzyltoluene as liquid organic hydrogen carrier were performed examining the catalytic performance. Differences when executing full particle measurements led to the conclusion that direct ink writing as shaping technique for catalyst carriers and the respective impregnation is highly beneficial as more complex shapes can be obtained, resulting in higher activities.

BackgroundThe 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 methodsLaboratory 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.ResultsWe 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.ConclusionsGBPC-CT allows quantitative differentiation of minimal-fat angiomyolipomas from pRCCs and ccRCCs in contrast to absorption-based imaging and clinical MRI.

Abstract X-ray dark-field imaging is a widely researched imaging technique, with many studies on samples of very different dimensions and at very different resolutions. However, retrieval of three-dimensional (3D) information for human thorax sized objects has not yet been demonstrated. We present a method, similar to classic tomography and tomosynthesis, to obtain 3D information in X-ray dark-field imaging. Here, the sample is moved through the divergent beam of a Talbot–Lau interferometer. Projections of features at different distances from the source seemingly move with different velocities over the detector, due to the cone beam geometry. The reconstruction of different focal planes exploits this effect. We imaged a chest phantom and were able to locate different features in the sample (e.g. the ribs, and two sample vials filled with water and air and placed in the phantom) to corresponding focal planes. Furthermore, we found that image quality and detectability of features is sufficient for image reconstruction with a dose of 68 μSv at an effective pixel size of $$0.357 \times {0.357}\,\mathrm{mm}^{2}$$ 0.357 × 0.357 mm 2 . Therefore, we successfully demonstrated that the presented method is able to retrieve 3D information in X-ray dark-field imaging.

Summary: Corumbella is a terminal Ediacaran tubular, benthic fossil of debated morphology, composition, and biological affinity. Here, we show that Corumbella had a biomineralized skeleton, with a bilayered construction of imbricated calcareous plates and rings (sclerites) yielding a cataphract organization, that enhanced flexibility. Each sclerite likely possessed a laminar microfabric with consistent crystallographic orientation, within an organic matrix. Original aragonitic mineralogy is supported by relict aragonite and elevated Sr (mean = ca. 11,800 ppm in central parts of sclerites). In sum, the presence of a polarisation axis, sclerites with a laminar microfabric, and a cataphract skeletal organization reminiscent of early Cambrian taxa, are all consistent with, but not necessarily indicative of, a bilaterian affinity. A cataphract skeleton with an inferred complex microstructure confirms the presence of controlled biomineralization in metazoans by the terminal Ediacaran, and offers insights into the evolution of development and ecology at the root of the ‘Cambrian radiation’.

Background and Purpose: Radiotherapy of thoracic tumours can lead to side effects in the lung, which may benefit from early diagnosis. We investigated the potential of X-ray dark-field computed tomography by a proof-of-principle murine study in a clinically relevant radiotherapeutic setting aiming at the detection of radiation-induced lung damage. Material and Methods: Six mice were irradiated with 20 Gy to the entire right lung. Together with five unirradiated control mice, they were imaged using computed tomography with absorption and dark-field contrast before and 16 weeks post irradiation. Mean pixel values for the right and left lung were calculated for both contrasts, and the right-to-left-ratio R of these means was compared. Radiologists also assessed the tomograms acquired 16 weeks post irradiation. Sensitivity, specificity, inter- and intra-reader accuracy were evaluated. Results: In absorption contrast the group-average of R showed no increase in the control group and increased by 7% (p = 0.005) in the irradiated group. In dark-field contrast, it increased by 2% in the control group and by 14% (p = 0.005) in the irradiated group. Specificity was 100% for both contrasts but sensitivity was almost four times higher using dark-field tomography. Two cases were missed by absorption tomography but were detected by dark-field tomography. Conclusions: The applicability of X-ray dark-field computed tomography for the detection of radiation-induced lung damage was demonstrated in a pre-clinical mouse model. The presented results illustrate the differences between dark-field and absorption contrast and show that dark-field tomography could be advantageous in future clinical settings.

Abstract We present a method to generate synthetic thorax radiographs with realistic nodules from CT scans, and a perfect ground truth knowledge. We evaluated the detection performance of nine radiologists and two convolutional neural networks in a reader study. Nodules were artificially inserted into the lung of a CT volume and synthetic radiographs were obtained by forward-projecting the volume. Hence, our framework allowed for a detailed evaluation of CAD systems’ and radiologists’ performance due to the availability of accurate ground-truth labels for nodules from synthetic data. Radiographs for network training (U-Net and RetinaNet) were generated from 855 CT scans of a public dataset. For the reader study, 201 radiographs were generated from 21 nodule-free CT scans with altering nodule positions, sizes and nodule counts of inserted nodules. Average true positive detections by nine radiologists were 248.8 nodules, 51.7 false positive predicted nodules and 121.2 false negative predicted nodules. The best performing CAD system achieved 268 true positives, 66 false positives and 102 false negatives. Corresponding weighted alternative free response operating characteristic figure-of-merits (wAFROC FOM) for the radiologists range from 0.54 to 0.87 compared to a value of 0.81 (CI 0.75–0.87) for the best performing CNN. The CNN did not perform significantly better against the combined average of the 9 readers (p = 0.49). Paramediastinal nodules accounted for most false positive and false negative detections by readers, which can be explained by the presence of more tissue in this area.

Abstract Cracked tooth syndrome (CTS) is a common clinical finding for teeth, it affects about 5% of all adults each year. The finding of CTS is favored by several risk factors such as restorations, bruxism, occlusion habits, and age. Treatment options range, depending on the severity, from no treatment at all to tooth extraction. Early diagnosis of CTS is crucial for optimal treatment and symptom reduction. There is no standard procedure for an evidence-based diagnosis up to date. The diagnosis is a challenge by the fact that the symptoms, including pain and sensitivity to temperature stimuli, cannot be clearly linked to the disease. Commonly used visual inspection does not provide in-depth information and is limited by the resolution of human eyes. This can be overcome by magnifying optics or contrast enhancers, but the diagnosis will still strongly rely on the practicians experience. Other methods are symptom reproduction with percussions, thermal pulp tests or bite tests. Dental X-ray radiography, as well as computed tomography, rarely detect cracks as they are limited in resolution. Here, we investigate X-ray dark-field tomography (XDT) for the detection of tooth microcracks. XDT simultaneously detects X-ray small-angle scattering (SAXS) in addition to the attenuation, whereas it is most sensitive to the micrometer regime. Since SAXS originates from gradients in electron density, the signal is sensitive to the sample morphology. Microcracks create manifold interfaces which lead to a strong signal. Therefore, it is possible to detect structural changes originating from subpixel-sized structures without directly resolving them. Together with complementary attenuation information, which visualizes comparatively large cracks, cracks are detected on all length-scales for a whole tooth in a non-destructive way. Hence, this proof-of principle study on three ex-vivo teeth shows the potential of X-ray scattering for evidence-based detection of cracked teeth.

Abstract Grating-based X-ray dark-field imaging is a novel imaging modality with enormous technical progress during the last years. It enables the detection of microstructure impairment as in the healthy lung a strong dark-field signal is present due to the high number of air-tissue interfaces. Using the experience from setups for animal imaging, first studies with a human cadaver could be performed recently. Subsequently, the first dark-field scanner for in-vivo chest imaging of humans was developed. In the current study, the optimal tube voltage for dark-field radiography of the thorax in this setup was examined using an anthropomorphic chest phantom. Tube voltages of 50–125 kVp were used while maintaining a constant dose-area-product. The resulting dark-field and attenuation radiographs were evaluated in a reader study as well as objectively in terms of contrast-to-noise ratio and signal strength. We found that the optimum tube voltage for dark-field imaging is 70 kVp as here the most favorable combination of image quality, signal strength, and sharpness is present. At this voltage, a high image quality was perceived in the reader study also for attenuation radiographs, which should be sufficient for routine imaging. The results of this study are fundamental for upcoming patient studies with living humans.

Abstract Although X‐ray contrast agents offer specific characteristics in terms of targeting and attenuation, their accumulation in the tissue on a cellular level is usually not known and difficult to access, as it requires high resolution and sensitivity. Here, quantitative near‐field ptychographic X‐ray computed tomography is demonstrated to assess the location of X‐ray stains at a resolution sufficient to identify intracellular structures by means of a basis material decomposition. On the example of two different X‐ray stains, the nonspecific iodine potassium iodide, and eosin Y, which mostly interacts with proteins and peptides in the cell cytoplasm, the distribution of the stains within the cells in murine kidney samples is assessed and compared to unstained samples with similar structural features. Quantitative nanoscopic stain concentrations are in good agreement with dual‐energy micro computed tomography measurements, the state‐of‐the‐art modality for material‐selective imaging. The presented approach can be applied to a variety of X‐ray stains advancing the development of X‐ray contrast agents.

Abstract Background Grating-based x-ray dark-field and phase-contrast imaging allow extracting information about refraction and small-angle scatter, beyond conventional attenuation. A step towards clinical translation has recently been achieved, allowing further investigation on humans. Methods After the ethics committee approval, we scanned the full body of a human cadaver in anterior-posterior orientation. Six measurements were stitched together to form the whole-body image. All radiographs were taken at a three-grating large-object x-ray dark-field scanner, each lasting about 40 s. Signal intensities of different anatomical regions were assessed. The magnitude of visibility reduction caused by beam hardening instead of small-angle scatter was analysed using different phantom materials. Maximal effective dose was 0.3 mSv for the abdomen. Results Combined attenuation and dark-field radiography are technically possible throughout a whole human body. High signal levels were found in several bony structures, foreign materials, and the lung. Signal levels were 0.25 ± 0.13 (mean ± standard deviation) for the lungs, 0.08 ± 0.06 for the bones, 0.023 ± 0.019 for soft tissue, and 0.30 ± 0.02 for an antibiotic bead chain. We found that phantom materials, which do not produce small-angle scatter, can generate a strong visibility reduction signal. Conclusion We acquired a whole-body x-ray dark-field radiograph of a human body in few minutes with an effective dose in a clinical acceptable range. Our findings suggest that the observed visibility reduction in the bone and metal is dominated by beam hardening and that the true dark-field signal in the lung is therefore much higher than that of the bone.

Cancer cells frequently harbour genetic aberrations that protect them from programmed cell death. Here, the authors show in non-small cell lung cancer that the anti-apoptotic gene MCL-1 is subject to copy number gains and that deletion of MCL-1 reduces tumour formation.

Summary: Background: Although advanced medical imaging technologies give detailed diagnostic information, a low-dose, fast, and inexpensive option for early detection of respiratory diseases and follow-ups is still lacking. The novel method of x-ray dark-field chest imaging might fill this gap but has not yet been studied in living humans. Enabling the assessment of microstructural changes in lung parenchyma, this technique presents a more sensitive alternative to conventional chest x-rays, and yet requires only a fraction of the dose applied in CT. We studied the application of this technique to assess pulmonary emphysema in patients with chronic obstructive pulmonary disease (COPD). Methods: In this diagnostic accuracy study, we designed and built a novel dark-field chest x-ray system (Technical University of Munich, Munich, Germany)—which is also capable of simultaneously acquiring a conventional thorax radiograph (7 s, 0·035 mSv effective dose). Patients who had undergone a medically indicated chest CT were recruited from the department of Radiology and Pneumology of our site (Klinikum rechts der Isar, Technical University of Munich, Munich, Germany). Patients with pulmonary pathologies, or conditions other than COPD, that might influence lung parenchyma were excluded. For patients with different disease stages of pulmonary emphysema, x-ray dark-field images and CT images were acquired and visually assessed by five readers. Pulmonary function tests (spirometry and body plethysmography) were performed for every patient and for a subgroup of patients the measurement of diffusion capacity was performed. Individual patient datasets were statistically evaluated using correlation testing, rank-based analysis of variance, and pair-wise post-hoc comparison. Findings: Between October, 2018 and December, 2019 we enrolled 77 patients. Compared with CT-based parameters (quantitative emphysema ρ=–0·27, p=0·089 and visual emphysema ρ=–0·45, p=0·0028), the dark-field signal (ρ=0·62, p

Abstract Background Although x-ray dark-field imaging has been intensively investigated for lung imaging in different animal models, there is very limited data about imaging features in the human lungs. Therefore, in this work, a reader study on nine post-mortem human chest x-ray dark-field radiographs was performed to evaluate dark-field signal strength in the lungs, intraobserver and interobserver agreement, and image quality and to correlate with findings of conventional x-ray and CT. Methods In this prospective work, chest x-ray dark-field radiography with a tube voltage of 70 kVp was performed post-mortem on nine humans (3 females, 6 males, age range 52–88 years). Visual quantification of dark-field and transmission signals in the lungs was performed by three radiologists. Results were compared to findings on conventional x-rays and 256-slice computed tomography. Image quality was evaluated. For ordinal data, median, range, and dot plots with medians and 95% confidence intervals are presented; intraobserver and interobserver agreement were determined using weighted Cohen κ. Results Dark-field signal grading showed significant differences between upper and middle (p = 0.004–0.016, readers 1–3) as well as upper and lower zones (p = 0.004–0.016, readers 1–2). Median transmission grading was indifferent between all lung regions. Intraobserver and interobserver agreements were substantial to almost perfect for grading of both dark-field (κ = 0.793–0.971 and κ = 0.828–0.893) and transmission images (κ = 0.790–0.918 and κ = 0.700–0.772). Pulmonary infiltrates correlated with areas of reduced dark-field signal. Image quality was rated good for dark-field images. Conclusions Chest x-ray dark-field images provide information of the lungs complementary to conventional x-ray and allow reliable visual quantification of dark-field signal strength.

Abstract Grating-based X-ray dark-field imaging is a novel imaging modality which has been refined during the last decade. It exploits the wave-like behaviour of X-radiation and can nowadays be implemented with existing X-ray tubes used in clinical applications. The method is based on the detection of small-angle X-ray scattering, which occurs e.g. at air-tissue-interfaces in the lung or bone-fat interfaces in spongy bone. In contrast to attenuation-based chest X-ray imaging, the optimal tube voltage for dark-field imaging of the thorax has not yet been examined. In this work, dark-field scans with tube voltages ranging from 60 to 120 kVp were performed on a deceased human body. We analyzed the resulting images with respect to subjective and objective image quality, and found that the optimum tube voltage for dark-field thorax imaging at the used setup is at rather low energies of around 60 to 70 kVp. Furthermore, we found that at these tube voltages, the transmission radiographs still exhibit sufficient image quality to correlate dark-field information. Therefore, this study may serve as an important guideline for the development of clinical dark-field chest X-ray imaging devices for future routine use.

Modern high-resolution X-ray microscopy techniques suffer from limited field-of-view or longer acquisition times. Here the authors use structured illumination to enable fast, full-field super-resolution transmission microscopy, even for optically thick specimens and at hard X-ray energies.

Abstract Background Tardigrades (water bears) are microscopic invertebrates of which the anatomy has been well studied using traditional techniques, but a comprehensive three-dimensional reconstruction has never been performed. In order to close this gap, we employed X-ray computed tomography (CT), a technique that is becoming increasingly popular in zoology for producing high-resolution, three-dimensional (3D) scans of whole specimens. While CT has long been used to scan larger samples, its use in some microscopic animals can be problematic, as they are often too small for conventional CT yet too large for high-resolution, optics-based soft X-ray microscopy. This size gap continues to be narrowed with advancements in technology, with high-resolution imaging now being possible using both large synchrotron devices and, more recently, laboratory-based instruments. Results Here we use a recently developed prototype lab-based nano-computed tomography device to image a 152 μm-long tardigrade at high resolution (200–270 nm pixel size). The resulting dataset allowed us to visualize the anatomy of the tardigrade in 3D and analyze the spatial relationships of the internal structures. Segmentation of the major structures of the body enabled the direct measurement of their respective volumes. Furthermore, we segmented every storage cell individually and quantified their volume distribution. We compare our measurements to those from published studies in which other techniques were used. Conclusions The data presented herein demonstrate the utility of CT imaging as a powerful supplementary tool for studies of tardigrade anatomy, especially for quantitative volume measurements. This nanoCT study represents the smallest complete animal ever imaged using CT, and offers new 3D insights into the spatial relationships of the internal organs of water bears.

Automatic evaluation of 3D volumes is a topic of importance in order to speed up clinical decision making. We describe a method to classify computed tomography scans on volume level for the presence of non-acute cerebral infarction. This is not a trivial task, as the lesions are often similar to other areas in the brain regarding shape and intensity. A three stage architecture is used for classification: 1) A cranial cavity segmentation network is developed, trained and applied. 2) Region proposals are generated 3) Connected regions are classified using a multi-resolution, densely connected 3D convolutional network. Mean area under curve values for subject level classification are 0.95 for the unstratified test set, 0.88 for stratification by patient age and 0.93 for stratification by CT scanner model. We use a partly segmented dataset of 555 scans of which 186 scans are used in the unstratified test set. Furthermore we examine possible dataset bias for scanner model and patient age parameters. We show a successful application of the proposed three-stage model for full volume classification. In contrast to black-box approaches, the convolutional network's decision can be further assessed by examination of intermediate segmentation results.

Abstract We describe the first dynamic and the first in vivo X-ray imaging studies successfully performed at a laser-undulator-based compact synchrotron light source. The X-ray properties of this source enable time-sequence propagation-based X-ray phase-contrast imaging. We focus here on non-invasive imaging for respiratory treatment development and physiological understanding. In small animals, we capture the regional delivery of respiratory treatment, and two measures of respiratory health that can reveal the effectiveness of a treatment; lung motion and mucociliary clearance. The results demonstrate the ability of this set-up to perform laboratory-based dynamic imaging, specifically in small animal models, and with the possibility of longitudinal studies.

Abstract Grating-based phase-contrast computed tomography (GBPC-CT) enables increased soft tissue differentiation, but often suffers from streak artifacts when performing high-sensitivity GBPC-CT of biomedical samples. Current GBPC-CT setups consist of one-dimensional gratings and hence allow to measure only the differential phase-contrast (DPC) signal perpendicular to the direction of the grating lines. Having access to the full two-dimensional DPC signal can strongly reduce streak artefacts showing up as characteristic horizontal lines in the reconstructed images. GBPC-CT with gratings tilted by 45° around the optical axis, combining opposed projections, and reconstructing with filtered backprojection is one method to retrieve the full three-dimensional DPC signal. This approach improves the quality of the tomographic data as already demonstrated at a synchrotron facility. However, additional processing and interpolation is necessary, and the approach fails when dealing with cone-beam geometry setups. In this work, we employ the tilted grating configuration with a laboratory GBPC-CT setup with cone-beam geometry and use statistical iterative reconstruction (SIR) with a forward model accounting for diagonal grating alignment. Our results show a strong reduction of streak artefacts and significant increase in image quality. In contrast to the prior approach our proposed method can be used in a laboratory environment due to its cone-beam compatibility.

Grating-based phase-contrast and dark-field imaging systems create intensity modulations that are usually modeled with sinusoidal functions to extract transmission, differential-phase shift, and scatter information. Under certain system-related conditions, the modulations become non-sinusoidal and cause artifacts in conventional processing. To account for that, we introduce a piecewise-defined periodic polynomial function that resembles the physical signal formation process, modeling convolutions of binary periodic functions. Additionally, we extend the model with an iterative expectation-maximization algorithm that can account for imprecise grating positions during phase-stepping. We show that this approach can process a higher variety of simulated and experimentally acquired data, avoiding most artifacts.

Abstract Grating-based X-ray interferometry offers vast potential for imaging materials and tissues that are not easily visualised using conventional X-ray imaging. Tomographic reconstruction based on X-ray interferometric data provides not only access to the attenuation coefficient of an object, but also the refractive index and information about ultra-small-angle scattering. This improved functionality comes at the cost of longer measurement times because existing projection-based signal extraction algorithms require not only a single measurement per projection angle but several with precise grating movements in between. This obstacle hinders the adaptation of grating-based interferometry into a continuously rotating gantry. Several solutions to this problem have been proposed but all suffer from major drawbacks. We present results using an iterative reconstruction algorithm working directly on the interferograms. The suggested direct approach enables improved image quality, since interpolations and unnecessary assumptions about the object are circumvented. Our results demonstrate that it is possible to successfully reconstruct the linear attenuation coefficient, the refractive index and the linear diffusion coefficient, which is a measure related to ultra-small-angle scattering, using a single measurement per projection angle and without any grating movements. This is a milestone for future clinical implementation of grating-based phase-contrast and dark-field contrast X-ray computed tomography.

Abstract X-ray chest radiography is an inexpensive and broadly available tool for initial assessment of the lung in clinical routine, but typically lacks diagnostic sensitivity for detection of pulmonary diseases in their early stages. Recent X-ray dark-field (XDF) imaging studies on mice have shown significant improvements in imaging-based lung diagnostics. Especially in the case of early diagnosis of chronic obstructive pulmonary disease (COPD), XDF imaging clearly outperforms conventional radiography. However, a translation of this technique towards the investigation of larger mammals and finally humans has not yet been achieved. In this letter, we present the first in-vivo XDF full-field chest radiographs (32 × 35 cm2) of a living pig, acquired with clinically compatible parameters (40 s scan time, approx. 80 µSv dose). For imaging, we developed a novel high-energy XDF system that overcomes the limitations of currently established setups. Our XDF radiographs yield sufficiently high image quality to enable radiographic evaluation of the lungs. We consider this a milestone in the bench-to-bedside translation of XDF imaging and expect XDF imaging to become an invaluable tool in clinical practice, both as a general chest X-ray modality and as a dedicated tool for high-risk patients affected by smoking, industrial work and indoor cooking.

Abstract We demonstrate the applicability of propagation-based X-ray phase-contrast imaging at a laser-assisted compact light source with known phantoms and the lungs and airways of a mouse. The Munich Compact Light Source provides a quasi-monochromatic beam with partial spatial coherence, and high flux relative to other non-synchrotron sources (up to 1010 ph/s). In our study we observe significant edge-enhancement and quantitative phase-retrieval is successfully performed on the known phantom. Furthermore the images of a small animal show the potential for live bio-imaging research studies that capture biological function using short exposures.

Abstract Dark-field imaging is a scattering-based X-ray imaging method that can be performed with laboratory X-ray tubes. The possibility to obtain information about unresolvable structures has already seen a lot of interest for both medical and material science applications. Unlike conventional X-ray attenuation, orientation dependent changes of the dark-field signal can be used to reveal microscopic structural orientation. To date, reconstruction of the three-dimensional dark-field signal requires dedicated, highly complex algorithms and specialized acquisition hardware. This severely hinders the possible application of orientation-dependent dark-field tomography. In this paper, we show that it is possible to perform this kind of dark-field tomography with common Talbot-Lau interferometer setups by reducing the reconstruction to several smaller independent problems. This allows for the reconstruction to be performed with commercially available software and our findings will therefore help pave the way for a straightforward implementation of orientation-dependent dark-field tomography.

Abstract Accounting for about 1.5 million deaths annually, lung cancer is the prevailing cause of cancer deaths worldwide, mostly associated with long-term smoking effects. Numerous small-animal studies are performed currently in order to better understand the pathogenesis of the disease and to develop treatment strategies. Within this letter, we propose to exploit X-ray dark-field imaging as a novel diagnostic tool for the detection of lung cancer on projection radiographs. Here, we demonstrate in living mice bearing lung tumors, that X-ray dark-field radiography provides significantly improved lung tumor detection rates without increasing the number of false-positives, especially in the case of small and superimposed nodules, when compared to conventional absorption-based imaging. While this method still needs to be adapted to larger mammals and finally humans, the technique presented here can already serve as a valuable tool in evaluating novel lung cancer therapies, tested in mice and other small animal models.

Abstract The aim of this study was to evaluate whether diagnosing pulmonary fibrosis with projection radiography can be improved by using X-ray dark-field radiograms. Pulmonary X-ray transmission and dark-field images of C57Bl/6N mice, either treated with bleomycin to induce pulmonary fibrosis or PBS to serve as controls, were acquired with a prototype grating-based small-animal scanner. Two blinded readers, both experienced radiologists and familiar with dark-field imaging, had to assess dark-field and transmission images for the absence or presence of fibrosis. Furthermore readers were asked to grade their stage of diagnostic confidence. Histological evaluation of the lungs served as the standard of reference in this study. Both readers showed a notably higher diagnostic confidence when analyzing the dark-field radiographs (p

Segmental, paired locomotory appendages are a characteristic feature of Panarthropoda—a diversified clade of moulting animals that includes onychophorans (velvet worms), tardigrades (water bears) and arthropods. While arthropods acquired a sclerotized exoskeleton and articulated limbs, onychophorans and tardigrades possess a soft body and unjointed limbs called lobopods, which they inherited from Cambrian lobopodians. To date, the origin and ancestral structure of the lobopods and their transformation into the jointed appendages are all poorly understood. We therefore combined high-resolution computed tomography with high-speed camera recordings to characterize the functional anatomy of a trunk lobopod from the onychophoran Euperipatoides rowelli. Three-dimensional reconstruction of the complete set of muscles and muscle fibres as well as non-muscular structures revealed the spatial relationship and relative volumes of the muscular, excretory, circulatory and nervous systems within the leg. Locomotory movements of individual lobopods of E. rowelli proved far more diverse than previously thought and might be governed by a complex interplay of 15 muscles, including one promotor, one remotor, one levator, one retractor, two depressors, two rotators, one flexor and two constrictors as well as muscles for stabilization and haemolymph control. We discuss the implications of our findings for understanding the evolution of locomotion in panarthropods.

Lung tissue causes significant small-angle X-ray scattering, which can be visualized with grating-based X-ray dark-field imaging. Structural lung diseases alter alveolar microstructure, which often causes a dark-field signal decrease. The imaging method provides benefits for diagnosis of such diseases in small-animal models, and was successfully used on porcine and human lungs in a fringe-scanning setup. Micro- and macroscopic changes occur in the lung during breathing, but their individual effects on the dark-field signal are unknown. However, this information is important for quantitative medical evaluation of dark-field thorax radiographs. To estimate the effect of these changes on the dark-field signal during a clinical examination, we acquired in vivo dark-field chest radiographs of two pigs at three ventilation pressures. Pigs were used due to the high degree of similarity between porcine and human lungs. To analyze lung expansion separately, we acquired CT scans of both pigs at comparable posture and ventilation pressures. Segmentation, masking, and forward-projection of the CT datasets yielded maps of lung thickness and logarithmic lung attenuation signal in registration with the dark-field radiographs. Upon correlating this data, we discovered approximately linear relationships between the logarithmic dark-field signal and both projected quantities for all scans. Increasing ventilation pressure strongly decreased dark-field extinction coefficients, whereas the ratio of lung dark-field and attenuation signal changed only slightly. Furthermore, we investigated ratios of dark-field and attenuation noise levels at realistic signal levels via calculations and phantom measurements. Dark-field contrast-to-noise ratio (CNR) per lung height was 5 to 10% of the same quantity in attenuation. We conclude that better CNR performance in the dark-field modality is typically due to greater anatomical noise in the conventional radiograph. Given the high physiological similarity of human and porcine lungs, the presented thickness-normalized, ventilation-dependent values allow estimation of dark-field activity of human lungs of variable size and inspiration, which facilitates the design of suitable clinical imaging setups.

The recent progress in photon-counting detector technology using high-Z semiconductor sensors provides new possibilities for spectral x-ray imaging. The benefits of the approach to extract spectral information directly from measurements in the projection domain are very advantageous for material science studies with x-rays as polychromatic artifacts like beam-hardening are handled properly. Since related methods require accurate knowledge of all energy-dependent system parameters, we utilize an adapted semi-empirical model, which relies on a simple calibration procedure. The method enables a projection-based decomposition of photon-counting raw-data into basis material projections. The objective of this paper is to investigate the method's performance applied to x-ray micro-CT with special focus on applications in material science and non-destructive testing. Projection-based dual-energy micro-CT is shown to be of good quantitative accuracy regarding material properties such as electron densities and effective atomic numbers. Furthermore, we show that the proposed approach strongly reduces beam-hardening artifacts and improves image contrast at constant measurement time.

ObjectivesTo evaluate the accuracy of Spectral Photon-Counting Computed Tomography (SPCCT) in the quantification of iodine concentrations and its potential for the differentiation between blood and iodine.MethodsTubes with blood and a concentration series of iodine were scanned with a preclinical SPCCT system (both in vitro and in an ex vivo bovine brain tissue sample). Iodine density maps (IDM) and virtual non-contrast (VNC) images were generated using the multi-bin spectral information to perform material decomposition. Region-of-interest (ROI) analysis was performed within the tubes to quantitatively determine the absolute content of iodine (mg/ml).ResultsIn conventional CT images, ROI analysis showed similar Hounsfield Unit (HU) values for the tubes with blood and iodine (59.9 ± 1.8 versus 59.2 ± 1.5). Iodine density maps enabled clear differentiation between blood and iodine in vitro, as well as in the bovine brain model. Quantitative measurements of the different iodine concentrations matched well with those of actual known concentrations even for very small iodine concentrations with values below 1mg/ml (RMSE = 0.19).ConclusionsSPCCT providing iodine maps and virtual non-contrast images allows material decomposition, differentiation between blood and iodine in vitro and ex vivo in a bovine brain model and reliably quantifies the iodine concentration.

ObjectiveAim of this study was, to demonstrate the feasibility of high-resolution grating-based X-ray phase-contrast computed tomography (PCCT) for quantitative assessment of cartilage.Materials and methodsIn an experimental setup, 12 osteochondral samples were harvested from n = 6 bovine knees (n = 2 each). From each knee, one cartilage sample was degraded using 2.5% Trypsin. In addition to PCCT and biomechanical cartilage stiffness measurements, 3T and 7T MRI was performed including MSME SE T2 and ME GE T2* mapping sequences for relaxationtime measurements. Paired t-tests and receiver operating characteristics (ROC) curves were used for statistical analyses.ResultsPCCT provided high-resolution images for improved morphological cartilage evaluation as compared to 3T and 7T MRI. Quantitative analyses revealed significant differences between the superficial and the deep cartilage layer for T2 mapping as well as for PCCT (P0.05). MRI and stiffness measurements showed significant differences between healthy and degraded osteochondral samples. Accuracy in the prediction of cartilage degradation was excellent for MRI and biomechanical analyses.ConclusionIn conclusion, high-resolution grating-based X-ray PCCT cartilage imaging is feasible. In addition to MRI and biomechanical analyses it provides complementary, water content independent, information for improved morphological and quantitative characterization of articular cartilage ultrastructure.

BackgroundThe extent of intraductal carcinoma in situ (DCIS) is commonly underestimated due to the discontinuous growth and lack of microcalcifications. Specimen radiography has been established to reduce the rate of re-excision. However, the predictive value for margin assessment with conventional specimen radiography for DCIS is low. In this study we assessed the potential of grating-based phase-contrast computed tomography (GBPC-CT) at conventional X-ray sources for specimen tomography of DCIS containing samples.Materials and methodsGBPC-CT was performed on four ex-vivo breast specimens containing DCIS and invasive carcinoma of non-specific type. Phase-contrast and absorption-based datasets were manually matched with corresponding histological slices as the standard of reference.ResultsMatching of CT images and histology was successful. GBPC-CT showed an improved soft tissue contrast compared to absorption-based images revealing more histological details in the same sections. Non-calcifying DCIS exceeding the invasive tumor could be correlated to areas of dilated bright ducts around the tumor.ConclusionsGBPC-CT imaging at conventional X-ray sources offers improved depiction quality for the imaging of breast tissue samples compared to absorption-based imaging, allows the identification of diagnostically relevant tissue details, and provides full three-dimensional assessment of sample margins.

The aim of this study is to assess whether perifocal bone marrow edema (BME) in patients with osteoid osteoma (OO) can be accurately detected on dual-layer spectral CT (DLCT) with three-material decomposition. To that end, 18 patients with OO (25.33 ± 12.44 years; 7 females) were pairwise-matched with 18 patients (26.72 ± 9.65 years; 9 females) admitted for suspected pathologies other than OO in the same anatomic location but negative imaging findings. All patients were examined with DLCT and MRI. DLCT data was decomposed into hydroxyapatite and water- and fat-equivalent volume fraction maps. Two radiologists assessed DLCT-based volume fraction maps for the presence of perifocal BME, using a Likert scale (1 = no edema; 2 = likely no edema; 3 = likely edema; 4 = edema). Accuracy, sensitivity, and specificity for the detection of BME on DLCT were analyzed using MR findings as standard of reference. For the detection of BME in patients with OO, DLCT showed a sensitivity of 0.92, a specificity of 0.94, and an accuracy of 0.92 for both radiologists. Interreader agreement for the assessment of BME with DLCT was substantial (weighted κ = 0.78; 95% CI, 0.59, 0.94). DLCT with material-specific volume fraction maps allowed accurate detection of BME in patients with OO. This may spare patients additional examinations and facilitate the diagnosis of OO.

High visibility (0.56) neutron-based multi-modal imaging with a Talbot–Lau interferometer at a wavelength of 1.6 Å is reported. A tomography scan of a strongly absorbing quartz geode sample was performed with both the neutron and an X-ray grating interferometer (70 kVp) for a quantitative comparison. Small scattering structures embedded in the absorbing silica matrix were well resolved in neutron dark-field CT slices with a spatial resolution of about 300 μm. Beneficial effects, such as monochromaticity and stronger penetration power of the used neutron radiation, helped to avoid the beam hardening-related artificial dark-field signal which was present in the X-ray data. Both dark-field modalities show mostly the same structures; however, some scattering features appear only in the neutron domain. Potential applications of combined X-ray and neutron multi-modal CT enabling one to probe both the nuclear and the electron density-related structural properties are discussed. strongly absorbing samples are now accessible for the dark-field modality by the use of thermal neutrons.

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.

Propagation-based phase-contrast tomography has become a valuable tool for visualization of three-dimensional biological samples, due to its high sensitivity and its potential in providing increased contrast between materials with similar absorption properties. We present a statistical iterative reconstruction algorithm for this imaging technique in the near-field regime. Under the assumption of a single material, the propagation of the x-ray wavefield—relying on the transport-of-intensity equation—is made an integral part of the tomographic reconstruction problem. With a statistical approach acting directly on the measured intensities, we find an unconstrained nonlinear optimization formulation whose solution yields the three-dimensional distribution of the sample. This formulation not only omits the intermediate step of retrieving the projected thicknesses but also takes the statistical properties of the measurements into account and incorporates prior knowledge about the sample in the form of regularization techniques. We show some advantages of this integrated approach compared to two-step approaches on data obtained using a commercially available x-ray micro-tomography system. In particular, we address one of the most considerable challenges of the imaging technique, namely, the artifacts arising from samples containing highly absorbing features. With the use of statistical weights in our noise model, we can account for these materials and recover features in the vicinity of the highly absorbing features that are lost in the conventional two-step approaches. In addition, the statistical modeling of our reconstruction approach will prove particularly beneficial in the ongoing transition of this imaging technique from synchrotron facilities to laboratory setups.

About one third of all deaths worldwide can be traced back to cardiovascular diseases. An interventional radiology procedure for their diagnosis is Digital Subtraction Angiography (DSA). An alternative to DSA is K-Edge subtraction (KES) imaging, which has been shown to be advantageous for moving organs and eliminating image artifacts caused by patient movement. As highly brilliant, monochromatic X-rays are required for this method, it has been limited to synchrotron facilities so far, restraining the feasibility in clinical routine. Compact synchrotron X-ray sources based on inverse Compton scattering, which have been evolving substantially over the past decade, provide X-rays with sufficient brilliance that meet spatial and financial requirements affordable in laboratory settings or for university hospitals. In this work, we demonstrate a first proof-of-principle K-edge subtraction imaging experiment using the Munich Compact Light Source (MuCLS), the first user-dedicated installation of a compact synchrotron X-ray source worldwide. It is shown experimentally that the technique of KES increases the visibility of small blood vessels overlaid by bone structures.

Disorders of the lungs such as chronic obstructive pulmonary disease (COPD) are a major cause of chronic morbidity and mortality and the third leading cause of death in the world. The absence of sensitive diagnostic tests for early disease stages of COPD results in under-diagnosis of this treatable disease in an estimated 60-85% of the patients. In recent years a grating-based approach to X-ray dark-field contrast imaging has shown to be very sensitive for the detection and quantification of pulmonary emphysema in small animal models. However, translation of this technique to imaging systems suitable for humans remains challenging and has not yet been reported. In this manuscript, we present the first X-ray dark-field images of in-situ human lungs in a deceased body, demonstrating the feasibility of X-ray dark-field chest radiography on a human scale. Results were correlated with findings of computed tomography imaging and autopsy. The performance of the experimental radiography setup allows acquisition of multi-contrast chest X-ray images within clinical boundary conditions, including radiation dose. Upcoming clinical studies will have to demonstrate that this technology has the potential to improve early diagnosis of COPD and pulmonary diseases in general.