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). MethodsIn 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 ( 7s, 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<0•0001) yields a stronger correlation with lung diffusion capacity in the evaluated cohort. Emphysema assessment based on dark-field chest x-ray features yields consistent conclusions with findings from visual CT image interpretation and shows improved diagnostic performance than conventional clinical tests characterising emphysema. Pair-wise comparison of corresponding test parameters between adjacent visual emphysema severity groups (CT-based, reference standard) showed higher effect sizes. The mean effect size over the group comparisons (absent-trace, trace-mild, mild-moderate, and moderate-confluent or advanced destructive visual emphysema grades) for the COPD assessment test score is 0•21, for forced expiratory volume in 1 s (FEV 1 )/functional vital capacity is 0•25, for FEV 1 % of predicted is 0•23, for residual volume % of predicted is 0•24, for CT emphysema index is 0•35, for dark-field signal homogeneity within lungs is 0•38, for dark-field signal texture within lungs is 0•38, and for darkfield-based emphysema severity is 0•42. Interpretation X-r...

Background: X-ray dark-field radiography takes advantage of the wave properties of x-rays, with a relatively high signal in the lungs due to the many air-tissue interfaces in the alveoli.Purpose: To describe the qualitative and quantitative characteristics of x-ray dark-field images in healthy human subjects. Materials and Methods:Between October 2018 and January 2020, patients of legal age who underwent chest CT as part of their diagnostic work-up were screened for study participation. Inclusion criteria were a normal chest CT scan, the ability to consent, and the ability to stand upright without help. Exclusion criteria were pregnancy, serious medical conditions, and changes in the lung tissue, such as those due to cancer, pleural effusion, atelectasis, emphysema, infiltrates, ground-glass opacities, or pneumothorax. Images of study participants were obtained by using a clinical x-ray dark-field prototype, recently constructed and commissioned at the authors' institution, to simultaneously acquire both attenuation-based and dark-field thorax radiographs. Each subject's total dark-field signal was correlated with his or her lung volume, and the dark-field coefficient was correlated with age, sex, weight, and height.Results: Overall, 40 subjects were included in this study (average age, 62 years 6 13 [standard deviation]; 26 men, 14 women). Normal human lungs have high signal, while the surrounding osseous structures and soft tissue have very low and no signal, respectively. The average dark-field signal was 2.5 m 21 6 0.4 of examined lung tissue. There was a correlation between the total dark-field signal and the lung volume (r = 0.61, P , .001). No difference was found between men and women (P = .78). Also, age (r = -0.18, P = .26), weight (r = 0.24, P = .13), and height (r = 0.01, P = .96) did not influence dark-field signal. Conclusion:This study introduces qualitative and quantitative values for x-ray dark-field imaging in healthy human subjects. The quantitative x-ray dark-field coefficient is independent from demographic subject parameters, emphasizing its potential in diagnostic assessment of the lung.

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MEDICAL PHYSICSC hronic obstructive pulmonary disease (COPD) is a major contributor to morbidity and mortality worldwide, with smoking and air pollution being the main risk factors. Its key components are chronic bronchitis and pulmonary emphysema (1). Early diagnosis of this disease is crucial for treatment and smoking cessation programs. However, current widely applied diagnostic tests do not work well for the early stages of this disease: Spirometry shows low sensitivity (2) and strongly depends on patient cooperation (3). Chest radiography lacks sensitivity and is not recommended for COPD diagnosis (4). Chest CT provides three-dimensional information and enables emphysema detection through classification of lung voxels by attenuation (in Hounsfield units) (5,6). An emphysematous voxel of lung tissue is defined as having an attenuation of less than 2950 HU at full inspiration. The resulting fraction of emphysematous lung tissue constitutes the emphysema index (EI). However, attenuation measurements of emphysema are known to vary with patient dose, section thickness, hardware, and reconstruction algorithm (7). Therefore, only an overall EI 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 6 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 = 20.54, ...