Dark-field X-ray imaging for the assessment of osteoporosis in human lumbar spine specimens.

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.

Dark-field chest X-ray imaging for the assessment of COVID-19-pneumonia.

BACKGROUND: Currently, alternative medical imaging methods for the assessment of pulmonary involvement in patients infected with COVID-19 are sought that combine a higher sensitivity than conventional (attenuation-based) chest radiography with a lower radiation dose than CT imaging. METHODS: Sixty patients with COVID-19-associated lung changes in a CT scan and 40 subjects without pathologic lung changes visible in the CT scan were included (in total, 100, 59 male, mean age 58 ± 14 years). All patients gave written informed consent. We employed a clinical setup for grating-based dark-field chest radiography, obtaining both a dark-field and a conventional attenuation image in one image acquisition. Attenuation images alone, dark-field images alone, and both displayed simultaneously were assessed for the presence of COVID-19-associated lung changes on a scale from 1 to 6 (1 = surely not, 6 = surely) by four blinded radiologists. Statistical analysis was performed by evaluation of the area under the receiver-operator-characteristics curves (AUC) using Obuchowski's method with a 0.05 level of significance. RESULTS: We show that dark-field imaging has a higher sensitivity for COVID-19-pneumonia than attenuation-based imaging and that the combination of both is superior to one imaging modality alone. Furthermore, a quantitative image analysis shows a significant reduction of dark-field signals for COVID-19-patients. CONCLUSIONS: Dark-field imaging complements and improves conventional radiography for the visualisation and detection of COVID-19-pneumonia.

Computed tomography (CT) imaging uses X-rays to obtain images of the inside of the body. It is used to look at lung damage in patients with COVID-19. However, CT imaging exposes the patient to a considerable amount of radiation. As radiation exposure can lead to the development of cancer, exposure should be minimised. Conventional plain X-ray imaging uses lower amounts of radiation but lacks sensitivity. We used dark-field chest X-ray imaging, which also uses low amounts of radiation, to assess the lungs of patients with COVID-19. Radiologists identified pneumonia in patients more easily from dark-field images than from usual plain X-ray images. We anticipate dark-field X-ray imaging will be useful to follow-up patients suspected of having lung damage.

Qualitative and Quantitative Assessment of Emphysema Using Dark-Field Chest Radiography.

Background Dark-field chest radiography allows for assessment of lung alveolar structure by exploiting wave optical properties of x-rays. Purpose To evaluate the qualitative and quantitative features of dark-field chest radiography in participants with pulmonary emphysema as compared with those in healthy control subjects. Materials and Methods In this prospective study conducted from October 2018 to October 2020, participants aged at least 18 years who underwent clinically indicated chest CT were screened for participation. Inclusion criteria were an ability to consent to the procedure and stand upright without help. Exclusion criteria were pregnancy, serious medical conditions, and any lung condition besides emphysema that was visible on CT images. Participants were examined with a clinical dark-field chest radiography prototype that simultaneously acquired both attenuation-based radiographs and dark-field chest radiographs. Dark-field coefficients were tested for correlation with each participant's CT-based emphysema index using the Spearman correlation test. Dark-field coefficients of adjacent groups in the semiquantitative Fleischner Society emphysema grading system were compared using a Wilcoxon Mann-Whitney U test. The capability of the dark-field coefficient to enable detection of emphysema was evaluated with receiver operating characteristics curve analysis. Results A total of 83 participants (mean age, 65 years ± 12 [standard deviation]; 52 men) were studied. When compared with images from healthy participants, dark-field chest radiographs in participants with emphysema had a lower and inhomogeneous dark-field signal intensity. The locations of focal signal intensity loss on dark-field images corresponded well with emphysematous areas found on CT images. The dark-field coefficient was negatively correlated with the quantitative CT-based emphysema index (r = -0.54, P < .001). Participants with Fleischner Society grades of mild, moderate, confluent, or advanced destructive emphysema exhibited a lower dark-field coefficient than those without emphysema (eg, 1.3 m-1 ± 0.6 for participants with confluent or advanced destructive emphysema vs 2.6 m-1 ± 0.4 for participants without emphysema; P < .001). The area under the receiver operating characteristic curve for detection of mild emphysema was 0.79. Conclusion Pulmonary emphysema leads to reduced signal intensity on dark-field chest radiographs, showing the technique has potential as a diagnostic tool in the assessment of lung diseases. © RSNA, 2022 See also the editorial by Hatabu and Madore in this issue.

Assessment of Inflation in a Human Cadaveric Lung with Dark-Field Chest Radiography.

Dark-field chest radiography signal intensity appeared to correlate with inflation status in a cadaveric lung.

Technical and dosimetric realization of in vivo x-ray microbeam irradiations at the Munich Compact Light Source.

PURPOSE: X-ray microbeam radiation therapy is a preclinical concept for tumor treatment promising tissue sparing and enhanced tumor control. With its spatially separated, periodic micrometer-sized pattern, this method requires a high dose rate and a collimated beam typically available at large synchrotron radiation facilities. To treat small animals with microbeams in a laboratory-sized environment, we developed a dedicated irradiation system at the Munich Compact Light Source (MuCLS). METHODS: A specially made beam collimation optic allows to increase x-ray fluence rate at the position of the target. Monte Carlo simulations and measurements were conducted for accurate microbeam dosimetry. The dose during irradiation is determined by a calibrated flux monitoring system. Moreover, a positioning system including mouse monitoring was built. RESULTS: We successfully commissioned the in vivo microbeam irradiation system for an exemplary xenograft tumor model in the mouse ear. By beam collimation, a dose rate of up to 5.3 Gy/min at 25 keV was achieved. Microbeam irradiations using a tungsten collimator with 50 µm slit size and 350 µm center-to-center spacing were performed at a mean dose rate of 0.6 Gy/min showing a high peak-to-valley dose ratio of about 200 in the mouse ear. The maximum circular field size of 3.5 mm in diameter can be enlarged using field patching. CONCLUSIONS: This study shows that we can perform in vivo microbeam experiments at the MuCLS with a dedicated dosimetry and positioning system to advance this promising radiation therapy method at commercially available compact microbeam sources. Peak doses of up to 100 Gy per treatment seem feasible considering a recent upgrade for higher photon flux. The system can be adapted for tumor treatment in different animal models, for example, in the hind leg.

3D grating-based X-ray phase-contrast computed tomography for high-resolution quantitative assessment of cartilage: An experimental feasibility study with 3T MRI, 7T MRI and biomechanical correlation.

OBJECTIVE: Aim 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 METHODS: In 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. RESULTS: PCCT 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 (P<0.05). No significant difference was detected for PCCT between healthy and degraded samples (P>0.05). 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. CONCLUSION: In 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.

Assessment of intraductal carcinoma in situ (DCIS) using grating-based X-ray phase-contrast CT at conventional X-ray sources: An experimental ex-vivo study.

BACKGROUND: The 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 METHODS: GBPC-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. RESULTS: Matching 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. CONCLUSIONS: GBPC-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.

Assessment of quantification accuracy and image quality of a full-body dual-layer spectral CT system.

The performance of a recently introduced spectral computed tomography system based on a dual-layer detector has been investigated. A semi-anthropomorphic abdomen phantom for CT performance evaluation was imaged on the dual-layer spectral CT at different radiation exposure levels (CTDIvol of 10 mGy, 20 mGy and 30 mGy). The phantom was equipped with specific low-contrast and tissue-equivalent inserts including water-, adipose-, muscle-, liver-, bone-like materials and a variation in iodine concentrations. Additionally, the phantom size was varied using different extension rings to simulate different patient sizes. Contrast-to-noise (CNR) ratio over the range of available virtual mono-energetic images (VMI) and the quantitative accuracy of VMI Hounsfield Units (HU), effective-Z maps and iodine concentrations have been evaluated. Central and peripheral locations in the field-of-view have been examined. For all evaluated imaging tasks the results are within the calculated theoretical range of the tissue-equivalent inserts. Especially at low energies, the CNR in VMIs could be boosted by up to 330% with respect to conventional images using iDose/spectral reconstructions at level 0. The mean bias found in effective-Z maps and iodine concentrations averaged over all exposure levels and phantom sizes was 1.9% (eff. Z) and 3.4% (iodine). Only small variations were observed with increasing phantom size (+3%) while the bias was nearly independent of the exposure level (±0.2%). Therefore, dual-layer detector based CT offers high quantitative accuracy of spectral images over the complete field-of-view without any compromise in radiation dose or diagnostic image quality.

Is multidetector CT-based bone mineral density and quantitative bone microstructure assessment at the spine still feasible using ultra-low tube current and sparse sampling?

OBJECTIVE: Osteoporosis diagnosis using multidetector CT (MDCT) is limited to relatively high radiation exposure. We investigated the effect of simulated ultra-low-dose protocols on in-vivo bone mineral density (BMD) and quantitative trabecular bone assessment. MATERIALS AND METHODS: Institutional review board approval was obtained. Twelve subjects with osteoporotic vertebral fractures and 12 age- and gender-matched controls undergoing routine thoracic and abdominal MDCT were included (average effective dose: 10 mSv). Ultra-low radiation examinations were achieved by simulating lower tube currents and sparse samplings at 50%, 25% and 10% of the original dose. BMD and trabecular bone parameters were extracted in T10-L5. RESULTS: Except for BMD measurements in sparse sampling data, absolute values of all parameters derived from ultra-low-dose data were significantly different from those derived from original dose images (p<0.05). BMD, apparent bone fraction and trabecular thickness were still consistently lower in subjects with than in those without fractures (p<0.05). CONCLUSION: In ultra-low-dose scans, BMD and microstructure parameters were able to differentiate subjects with and without vertebral fractures, suggesting osteoporosis diagnosis is feasible. However, absolute values differed from original values. BMD from sparse sampling appeared to be more robust. This dose-dependency of parameters should be considered for future clinical use. KEY POINTS: • BMD and quantitative bone parameters are assessable in ultra-low-dose in vivo MDCT scans. • Bone mineral density does not change significantly when sparse sampling is applied. • Quantitative trabecular bone microstructure measurements are sensitive to dose reduction. • Osteoporosis subjects could be differentiated even at 10% of original dose. • Radiation exposure should be considered when comparing quantitative bone parameters.

Ex Vivo Assessment of Coronary Atherosclerotic Plaque by Grating-Based Phase-Contrast Computed Tomography: Correlation With Optical Coherence Tomography.

OBJECTIVES: The aim of this study was to determine the diagnostic accuracy of grating-based phase-contrast computed tomography (gb-PCCT) to classify and quantify coronary vessel characteristics in comparison with optical coherence tomography (OCT) and histopathology in an ex vivo setting. MATERIALS AND METHODS: After excision from 5 heart specimens, 15 human coronary arteries underwent gb-PCCT examination using an experimental imaging setup consisting of a rotating molybdenum anode x-ray tube, a Talbot-Lau grating interferometer, and a single photon counting detector. Subsequently, all vessels were imaged by OCT and histopathologically processed. Optical coherence tomography, gb-PCCT, and histopathology images were manually matched using anatomical landmarks. Optical coherence tomography and gb-PCCT were reviewed by 2 independent observers blinded to histopathology. Vessel, lumen, and plaque area were measured, and plaque characteristics (lipid rich, calcified, and fibrous) were determined for each section. Measures of diagnostic accuracy were derived, applying histopathology as the standard of reference. RESULTS: Of a total of 286 assessed cross sections, 241 corresponding sections were included in the statistical analysis. Quantitative measures derived from gb-PCCT were significantly higher than from OCT (P < 0.001) and were strongly correlated with histopathology (Pearson r ≥0.85 for gb-PCCT and ≥0.61 for OCT, respectively). Results of Bland-Altman analysis demonstrated smaller mean differences between OCT and histopathology than for gb-PCCT and histopathology. Limits of agreement were narrower for gb-PCCT with regard to lumen area, for OCT with regard to plaque area, and were comparable with regard to vessel area. Based on histopathology, 228/241 (94.6%) sections were classified as fibrous, calcified, or lipid rich. The diagnostic accuracy of gb-PCCT was excellent for the detection of all plaque components (sensitivity, ≥0.95; specificity, ≥0.94), whereas the results for OCT showed sensitivities of ≥0.73 and specificities of ≥0.66. CONCLUSIONS: In this ex vivo setting, gb-PCCT provides excellent results in the assessment of coronary atherosclerotic plaque characteristics and vessel dimensions in comparison to OCT and histopathology. Thus, the technique may serve as adjunct nondestructive modality for advanced plaque characterization in an experimental setting.

Improved In vivo Assessment of Pulmonary Fibrosis in Mice using X-Ray Dark-Field Radiography.

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease with a median life expectancy of 4-5 years after initial diagnosis. Early diagnosis and accurate monitoring of IPF are limited by a lack of sensitive imaging techniques that are able to visualize early fibrotic changes at the epithelial-mesenchymal interface. Here, we report a new x-ray imaging approach that directly visualizes the air-tissue interfaces in mice in vivo. This imaging method is based on the detection of small-angle x-ray scattering that occurs at the air-tissue interfaces in the lung. Small-angle scattering is detected with a Talbot-Lau interferometer, which provides the so-called x-ray dark-field signal. Using this imaging modality, we demonstrate-for the first time-the quantification of early pathogenic changes and their correlation with histological changes, as assessed by stereological morphometry. The presented radiography method is significantly more sensitive in detecting morphological changes compared with conventional x-ray imaging, and exhibits a significantly lower radiation dose than conventional x-ray CT. As a result of the improved imaging sensitivity, this new imaging modality could be used in future to reduce the number of animals required for pulmonary research studies.

Assessment of grating-based X-ray phase-contrast CT for differentiation of invasive ductal carcinoma and ductal carcinoma in situ in an experimental ex vivo set-up.

OBJECTIVE: Limited contrast between healthy and tumour tissue is a limiting factor in mammography and CT of the breast. Phase-contrast computed tomography (PC-CT) provides improved soft-tissue contrast compared with absorption-based techniques. In this study, we assessed the technical feasibility of grating-based PC-CT imaging of the breast for characterisation of ductal carcinoma in situ (DCIS). METHODS: Grating-based PC-CT was performed on one breast specimen containing an invasive ductal carcinoma and DCIS using monochromatic radiation of 23 keV. Phase-contrast and absorption-based images were compared qualitatively and quantitatively with histopathology in a blinded fashion. RESULTS: Grating-based PC-CT showed improved differentiation of soft-tissue components. Circular structures of high phase-shift contrast corresponding to the walls of the dilated ductuli of the DCIS were visualised with a contrast-to-noise ratio (CNR) of 9.6 using PC-CT but were not detectable on absorption-based images (CNR = 0.27). The high phase-shift structures of the dilated ductuli were identifiable in the PC-CT volume data set allowing for 3D characterisation of DCIS. CONCLUSIONS: Our results indicate that unlike conventional CT, grating-based PC-CT may allow the differentiation between invasive carcinoma and intraductal carcinoma and healthy breast tissue and provide 3D visualisation of DCIS.