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Objective Assessing the advantage of x-ray dark-field contrast over x-ray transmission contrast in radiography for the detection of developing radiation-induced lung damage in mice. Methods Two groups of female C57BL/6 mice (irradiated and control) were imaged obtaining both contrasts monthly for 28 weeks post irradiation. Six mice received 20 Gy of irradiation to the entire right lung sparing the left lung. The control group of six mice was not irradiated. A total of 88 radiographs of both contrasts were evaluated for both groups based on average values for two regions of interest, covering (irradiated) right lung and healthy left lung. The ratio of these average values, R, was distinguished between healthy and damaged lungs for both contrasts. The time-point when deviations of R from healthy lung exceeded 3σ was determined and compared among contrasts. The Wilcoxon-Mann-Whitney test was used to test against the null hypothesis that there is no difference between both groups. A selection of 32 radiographs was assessed by radiologists. Sensitivity and specificity were determined in order to compare the diagnostic potential of both contrasts. Inter-reader and intra-reader accuracy were rated with Cohen’s kappa. Results Radiation-induced morphological changes of lung tissue caused deviations from the control group that were measured on average 10 weeks earlier with x-ray dark-field contrast than with x-ray transmission contrast. Sensitivity, specificity, and accuracy doubled using dark-field radiography. Conclusion X-ray dark-field radiography detects morphological changes of lung tissue associated with radiation-induced damage earlier than transmission radiography in a pre-clinical mouse model. Key Points • Significant deviations from healthy lung due to irradiation were measured after 16 weeks with x-ray dark-field radiography (p = 0.004). • Significant deviations occur on average 10 weeks earlier for x-ray dark-field radiography in comparison to x-ray transmission radiography. • Sensitivity and specificity doubled when using x-ray dark-field radiography instead of x-ray transmission radiography.

Grating-based dark-field interferometry can be realized with lab-based, low-brilliance X-ray sources and provides scattering information of sample structures below the detector pixel size. This unique property allows promising medical imaging applications, especially for lung diseases. Structural damage in lung tissue caused by pulmonary emphysema or pulmonary carcinoma could be observed in radiographs by changes in the dark-field signal with high sensitivity at early stages, in contrast to the conventional absorption signal. Currently, the standard for diagnosis in the clinical routine of pulmonary diseases is absorption CT. The assessment of a larger number of samples with in-vivo dark-field CT is limited by the rather long scan times, the order of 2 hours, that are required to obtain sufficient CT data quality. In this work, a prototype in-vivo, small-animal, dark-field CT is optimized with respect to CT measurements with the following: usage of an iterative reconstruction algorithm for the reduction of undersampling artifacts, a rearranged data acquisition scheme with reduced amount of dead time, and thinned gratings and curved grating geometry for more efficient utilization of the 37 kV X-ray flux. The device performance is evaluated with noiseeffective dose measurements, image contrast-to-noise ratio, interferometry visibility across the field-of-view, and a reduced measurement time of 40 minutes with a deposited dose of 85 mGy.

In this study we aim to evaluate the assessment of bronchial pathologies in a murine model of lung transplantation with grating-based X-ray interferometry in vivo. Imaging was performed using a dedicated grating-based small-animal X-ray dark-field and phase-contrast scanner. While the contrast modality of the dark-field signal already showed several promising applications for diagnosing various types of pulmonary diseases, the phase-shifting contrast mechanism of the phase contrast has not yet been evaluated in vivo. For this purpose, qualitative analysis of phase-contrast images was performed and revealed pathologies due to previous lung transplantation, such as unilateral bronchial stenosis or bronchial truncation. Dependent lung parenchyma showed a strong loss in dark-field and absorption signal intensity, possibly caused by several post transplantational pathologies such as atelectasis, pleural effusion, or pulmonary infiltrates. With this study, we are able to show that bronchial pathologies can be visualized in vivo using conventional X-ray imaging when phase-contrast information is analysed. Absorption and dark-field images can be used to quantify the severity of lack of ventilation in the affected lung.

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