X-ray dark-field imaging of the human lung-A feasibility study on a deceased body.

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.

Depiction of pneumothoraces in a large animal model using x-ray dark-field radiography.

The aim of this study was to assess the diagnostic value of x-ray dark-field radiography to detect pneumothoraces in a pig model. Eight pigs were imaged with an experimental grating-based large-animal dark-field scanner before and after induction of a unilateral pneumothorax. Image contrast-to-noise ratios between lung tissue and the air-filled pleural cavity were quantified for transmission and dark-field radiograms. The projected area in the object plane of the inflated lung was measured in dark-field images to quantify the collapse of lung parenchyma due to a pneumothorax. Means and standard deviations for lung sizes and signal intensities from dark-field and transmission images were tested for statistical significance using Student's two-tailed t-test for paired samples. The contrast-to-noise ratio between the air-filled pleural space of lateral pneumothoraces and lung tissue was significantly higher in the dark-field (3.65 ± 0.9) than in the transmission images (1.13 ± 1.1; p = 0.002). In case of dorsally located pneumothoraces, a significant decrease (-20.5%; p > 0.0001) in the projected area of inflated lung parenchyma was found after a pneumothorax was induced. Therefore, the detection of pneumothoraces in x-ray dark-field radiography was facilitated compared to transmission imaging in a large animal model.

In-vivo X-ray Dark-Field Chest Radiography of a Pig.

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.

Characterization of Cystic Lesions by Spectral Mammography: Results of a Clinical Pilot Study.

OBJECTIVES: Round lesions are a common mammographic finding, which can contribute more than 20% of overall recalls at screening. Discrimination of cystic fluid from solid tissue by spectral x-ray imaging has been demonstrated in specimen experiments. This work translates these results into a clinical pilot study to investigate the feasibility of discriminating cystic from solid lesions using spectral mammography. MATERIALS AND METHODS: Women undergoing mammography as part of their routine diagnostic workup were consented for analysis of spectral information obtained from a photon-counting mammography system. Images were analyzed retrospectively after diagnosis was confirmed with ultrasound and pathology. Well-defined solitary lesions were delineated independently by 3 expert radiologists. A breast lesion model is generated from the spectral mammography data using the energy-dependent x-ray attenuation of cyst fluid, carcinoma, and adipose and glandular tissue. From the breast lesion model, 2 spectral features are computed and combined in a 2-feature discrimination algorithm, which is evaluated in an analysis of the receiver operating characteristic curve for the task of identifying solid lesions ("positive result"). Expected outcomes on a screening population are extrapolated from this pilot study by cross-validation with bootstrapping using a 95% confidence interval (CI). RESULTS: The 2-feature discrimination algorithm was evaluated on the set of 119 eligible lesions (62 solids, 57 cysts) of diameter greater than 10 mm. The area under the receiver operating characteristic curve (AUC) was 0.88 with a specificity of 61% at the 99% sensitivity level on average over all expert radiologists. Cross-validation with bootstrapping of the clinical data revealed an AUC of 0.89 (95% CI, 0.79-0.96) and a specificity of 56% (95% CI, 33%-78%) when operating the algorithm at the 99% sensitivity level. CONCLUSIONS: Discriminating cystic from solid lesions with spectral mammography demonstrates promising results with the potential to reduce mammographic recalls. It is estimated that for each missed cancer at least 625 cystic lesions would have been correctly identified and hence would not have been needed to be recalled. Our results justify undertaking a larger reader study to refine the algorithm and determine clinically relevant thresholds to allow safe classification of cystic lesions by spectral mammography.

A study on mastectomy samples to evaluate breast imaging quality and potential clinical relevance of differential phase contrast mammography.

OBJECTIVES: Differential phase contrast and scattering-based x-ray mammography has the potential to provide additional and complementary clinically relevant information compared with absorption-based mammography. The purpose of our study was to provide a first statistical evaluation of the imaging capabilities of the new technique compared with digital absorption mammography. MATERIALS AND METHODS: We investigated non-fixed mastectomy samples of 33 patients with invasive breast cancer, using grating-based differential phase contrast mammography (mammoDPC) with a conventional, low-brilliance x-ray tube. We simultaneously recorded absorption, differential phase contrast, and small-angle scattering signals that were combined into novel high-frequency-enhanced images with a dedicated image fusion algorithm. Six international, expert breast radiologists evaluated clinical digital and experimental mammograms in a 2-part blinded, prospective independent reader study. The results were statistically analyzed in terms of image quality and clinical relevance. RESULTS: The results of the comparison of mammoDPC with clinical digital mammography revealed the general quality of the images to be significantly superior (P < 0.001); sharpness, lesion delineation, as well as the general visibility of calcifications to be significantly more assessable (P < 0.001); and delineation of anatomic components of the specimens (surface structures) to be significantly sharper (P < 0.001). Spiculations were significantly better identified, and the overall clinically relevant information provided by mammoDPC was judged to be superior (P < 0.001). CONCLUSIONS: Our results demonstrate that complementary information provided by phase and scattering enhanced mammograms obtained with the mammoDPC approach deliver images of generally superior quality. This technique has the potential to improve radiological breast diagnostics.