| 1. |
- Einarsdóttir, Hildur, et al.
(författare)
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Computer-aided diagnosis of pulmonary diseases using x-ray darkfield radiography
- 2015
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Ingår i: Physics in Medicine and Biology. - : IOP Publishing. - 0031-9155 .- 1361-6560. ; 60:24, s. 9253-9268
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Tidskriftsartikel (refereegranskat)abstract
- In this work we develop a computer-aided diagnosis (CAD) scheme for classification of pulmonary disease for grating-based x-ray radiography. In addition to conventional transmission radiography, the grating-based technique provides a dark-field imaging modality, which utilizes the scattering properties of the x-rays. This modality has shown great potential for diagnosing early stage emphysema and fibrosis in mouse lungs in vivo. The CAD scheme is developed to assist radiologists and other medical experts to develop new diagnostic methods when evaluating grating-based images. The scheme consists of three stages: (i) automatic lung segmentation; (ii) feature extraction from lung shape and dark-field image intensities; (iii) classification between healthy, emphysema and fibrosis lungs. A study of 102 mice was conducted with 34 healthy, 52 emphysema and 16 fibrosis subjects. Each image was manually annotated to build an experimental dataset. System performance was assessed by: (i) determining the quality of the segmentations; (ii) validating emphysema and fibrosis recognition by a linear support vector machine using leave-one-out cross-validation. In terms of segmentation quality, we obtained an overlap percentage (Ω) 92.63 ± 3.65%, Dice Similarity Coefficient (DSC) 89.74 ± 8.84% and Jaccard Similarity Coefficient 82.39 ± 12.62%. For classification, the accuracy, sensitivity and specificity of diseased lung recognition was 100%. Classification between emphysema and fibrosis resulted in an accuracy of 93%, whilst the sensitivity was 94% and specificity 88%. In addition to the automatic classification of lungs, deviation maps created by the CAD scheme provide a visual aid for medical experts to further assess the severity of pulmonary disease in the lung, and highlights regions affected.
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| 2. |
- Hellbach, Katharina, et al.
(författare)
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In Vivo Dark-Field Radiography for Early Diagnosis and Staging of Pulmonary Emphysema.
- 2015
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Ingår i: Investigative Radiology. - 0020-9996. ; 50:7, s. 430-435
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate the suitability of in vivo x-ray dark-field radiography for early-stage diagnosis of pulmonary emphysema in mice. Furthermore, we aimed to analyze how the dark-field signal correlates with morphological changes of lung architecture at distinct stages of emphysema.
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| 3. |
- Ulke, Henrik M, et al.
(författare)
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The Oncogene ECT2 Contributes to a Hyperplastic, Proliferative Lung Epithelial Cell Phenotype in Idiopathic Pulmonary Fibrosis
- 2019
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Ingår i: American Journal of Respiratory Cell and Molecular Biology. - 1535-4989. ; 61:6, s. 713-726
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Tidskriftsartikel (refereegranskat)abstract
- Idiopathic pulmonary fibrosis (IPF) and lung cancer represent progressive lung diseases with a poor prognosis. IPF represents a risk factor for the development of lung cancer, and the incidence of lung cancer is increased in patients with IPF. Disease pathogenesis of IPF and lung cancer involves common genetic alterations, dysregulated pathways, and the emergence of hyperplastic and metaplastic epithelial cells. Here, we aimed to identify novel, common mediators that might contribute to epithelial cell reprogramming in IPF. Gene set enrichment analysis (GSEA) of publicly available non-small cell lung cancer (NSCLC) and IPF datasets revealed a common pattern of misregulated genes, linked to cell proliferation and transformation. The oncogene epithelial cell transforming sequence 2 (ECT2), a guanine nucleotide exchange factor (GEF) for Rho GTPases, was highly enriched in both, IPF and NSCLC, compared to non-diseased controls. Increased expression of ECT2 was verified by qPCR and Western blotting in bleomycin-induced lung fibrosis and human IPF tissue. Immunohistochemistry demonstrated strong expression of ECT2 staining in hyperplastic type II alveolar epithelial (ATII) cells in IPF, as well as its colocalization with PCNA, a well-known proliferation marker. Increased ECT2 expression coincided with enhanced proliferation of primary mouse ATII cells as analyzed by flow cytometric analysis. ECT2 knockdown in ATII cells resulted in decreased proliferation and collagen I expression in vitro. These data suggest that the oncogene ECT2 contributes to epithelial cell reprogramming in IPF and further underline the hyperplastic, proliferative ATII cell as a potential target in patients with IPF and lung cancer.
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| 4. |
- Yaroshenko, Andre, et al.
(författare)
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Improved In vivo Assessment of Pulmonary Fibrosis in Mice using X-Ray Dark-Field Radiography.
- 2015
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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