III.

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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...

Purpose Several anatomic risk factors associated with patellofemoral disorders have been described. The purpose of this study was to analyze the relationship between bony parameters commonly used to analyze and define patellofemoral malalignment. Methods Patients with patellofemoral disorders presenting between 2016 and 2018 who underwent a standardized radiographic workup including conventional radiographs, weight bearing full-leg radiographs, magnetic resonance imaging (MRI) of the knee, and torsional analysis using hip-knee-ankle MRI were initially included. Patients with a history of lower extremity fracture and a history of surgical procedures affecting bony alignment or partial/total arthroplasty were subsequently excluded. Radiographs and MRI of all included patients were analyzed by four independent observers. Parameters of interest were: femoral torsion, tibial torsion, trochlear dysplasia, tibial tuberosity-trochlear groove (TT-TG) distance, and frontal mechanical axis. All parameters were compared between patients with low grade and high grade trochlear dysplasia as well as between female and male patients. Correlation of continuous variables was assessed with the Pearson correlation coefficient. A binary logistic regression model was used for the calculation of odds ratio between different parameters. Interclass correlation coefficients (ICC) were calculated to determine the interobserver reproducibility. Results A total of 151 patients could be included for detailed analysis. Group comparison revealed that patients with high grade trochlear dysplasia showed significantly higher values for femoral torsion (low grade: 9.8° ± 11.0°, high grade: 16.8° ± 11.5°; p < 0.001) and significantly higher values for TT-TG distance (low grade: 19.0 mm ± 5.0 mm, high grade: 21.9 mm ± 5.4 mm; p = 0.002). No significant difference was found for age, tibial torsion, and frontal mechanical axis. With regard to gender, female patients had higher values for femoral torsion (female: 15.6° ± 11.3°, male: 11.0° ± 12.7°; p = 0.044). The correlation analysis found significant correlation between femoral torsion and tibial torsion (r = 0.244, p = 0.003), femoral torsion and TT-TG distance (r = 0.328, p < 0.001), femoral torsion and frontal mechanical axis (r = 0.291, p < 0.001), and tibial torsion and TT-TG distance (r = 0.182, p = 0.026). Conclusion Bony malalignment in patients with patellofemoral disorder is a complex problem given the significant correlation between femoral and tibial torsion, trochlear dysplasia, TT-TG distance, and frontal mechanical axis. Advanced imaging to analyze rotational and frontal plane alignment is recommended in patients with trochlear dysplasia and/or increased TT-TG on standard radiographs and knee MRI. Understanding of the bony pathology in patellofemoral disorders is key to improve the therapeutic and surgical decision. Level of evidence III, retrospective cohort study.

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 (CTDI vol 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.

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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.

This prospective trial aimed to investigate whether tumor‐specific cKIT and PDGFRA mutations can be detected and quantified in circulating tumor (ct)DNA in patients with active GIST, and whether detection indicates disease activity. We included 25 patients with active disease and cKIT or PDGFRA mutations detected in tissue. Mutant ctDNA was detected in the peripheral blood plasma using allele‐specific ligation (L‐)PCR and droplet digital (d)PCR. CtDNA harboring tumor‐specific cKIT or PDGFRA mutations was detected at least once in 16 out of 25 patients using L‐PCR (64%) and in 20 out of 25 patients with dPCR (80%). Using dPCR, the absolute numbers of ctDNA fragments (DNA copies/ml) and the mutant allele frequency (MAF; in percent of wild‐type control) strongly correlated with tumor size expressed as RECIST1.1 sum of diameter (SOD) in mm (ρ = 0.3719 and 0.408, respectively, p < 0.0001) and response status (ρ = 0.3939 and 0.392, respectively, p < 0.0001 and p < 0.001). Specificity of dPCR for detection of progression was 79.2% with a sensitivity of 55.2% and dPCR discriminated CR from active disease with a specificity of 96% and s sensitivity of 44.7%. With L‐PCR, correlations of MAF with tumor size and response status were less prominent. Serial ctDNA measurement reflected individual disease courses over time. Targeted panel sequencing of four patients detected additional driver mutations in all cases and secondary resistance mutations in two cases. Thus, ctDNA indicates disease activity in patients with GIST and should be incorporated as companion biomarker in future prospective trials.