X-ray Dark-field Radiography - In-Vivo Diagnosis of Lung Cancer in Mice

Scherer, Kai; Yaroshenko, Andre; Bölükbas, Deniz A.; Gromann, Lukas B.; Hellbach, Katharina; Meinel, Felix G.; Braunagel, Margarita; Berg, Jens von; Eickelberg, Oliver; Reiser, Maximilian; Pfeiffer, Franz; Meiners, Silke; Herzen, Julia

doi:10.1038/s41598-017-00489-x

Cited by 68 publications

(55 citation statements)

References 47 publications

(51 reference statements)

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“…This observation is supported by the aforementioned recent study investigating dark-field imaging in a mouse model of neonatal lung injury due to mechanical ventilation and supplementation of oxygen-enriched gas [ 18 ]. Additionally, in a mouse model of lung cancer, regions with cancerous tissue show a reduced air:tissue volume ratio due to uncontrolled cell proliferation and loss of alveolar space and therefore X-ray scattering is strongly reduced [ 30 ]. Based on previous publications in small-animal models, it is unlikely that the overall conclusions of our study are compromised by the fact that imaging was performed on a dead human body rather than living subject.…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2018

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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.

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Section: Resultsmentioning

confidence: 99%

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

et al. 2018

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“…Several studies on pulmonary diseases in mouse models have demonstrated dark-field radiography of the lung to improve the diagnosis of pulmonary emphysema 1 – 3 , fibrosis 4 , bronchopulmonary dysplasia 5 , lung cancer 6 , and pneumothoraces 7 . Investigation of animal models with chest dimensions comparable to humans is an essential step toward the potential in vivo implementation of this new imaging modality in a clinical setting.…”

Section: Introductionmentioning

confidence: 99%

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

Hellbach

Baehr

Marco

et al. 2018

Sci Rep

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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.

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“…A dark-field signal is generated when sub-pixel structures scatter the x-ray wavefield, and the strength of this signal will depend on the number and size of scattering structures [21,22]. As a result of the many scattering structures in the lung the technique can provide high contrast lung images, provided the temporal resolution is not important [23,24,25,26,27], making some clinical applications feasible [28,29]. We considered if there was potential for the dark-field modality to reveal the presence of treatment, noting that the treatment delivery is not a repeated motion.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Visualizing treatment delivery and deposition in mouse lungs using in vivo x-ray imaging

Gradl

Dierolf

Yang³

et al. 2019

Journal of Controlled Release

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The complexity of lung diseases makes pre-clinical in vivo respiratory research in mouse lungs of great importance for a better understanding of physiology and therapeutic effects. Synchrotron-based imaging has been successfully applied to lung research studies, however longitudinal studies can be difficult to perform due to limited facility access. Laboratory-based x-ray sources, such as inverse Compton x-ray sources, remove this access limitation and open up new possibilities for pre-clinical small-animal lung research at high spatial and temporal resolution. The in vivo visualization of drug deposition in mouse lungs is of interest, particularly in longitudinal research, because the therapeutic outcome is not only dependent on the delivered dose of the drug, but also on the spatial distribution of the drug. An additional advantage of this approach, when compared to other imaging techniques, is that anatomic and dynamic information is collected simultaneously. Here we report the use of dynamic x-ray phase-contrast imaging to observe pulmonary drug delivery via liquid instillation, and by inhalation of micro-droplets. Different liquid volumes (4 l  , 20 l  , 50 l ) were tested and a range of localized and global distributions were observed with a temporal resolution of up to 1.5 fps. The in vivo imaging results were confirmed by ex vivo x-ray and fluorescence imaging. This ability to visualize pulmonary substance deposition in live small animals has provided a better understanding of the two key methods of delivery; instillation and nebulization.

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X-ray Dark-field Radiography - In-Vivo Diagnosis of Lung Cancer in Mice

Cited by 68 publications

References 47 publications

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

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

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

Visualizing treatment delivery and deposition in mouse lungs using in vivo x-ray imaging

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