Early detection of radiation-induced lung damage with X-ray dark-field radiography in mice

Abstract

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.

Whole-body x-ray dark-field radiography of a human cadaver

“…In past small animal studies, x-ray dark-field imaging showed a potential benefit in diagnosing lung diseases [31][32][33][34][35][36][37][38][39][40][41][42]54]. Subsequent large animal and human cadaver measurements showed the possibility to translate x-ray dark-field radiography to the human scale [43][44][45][46], and a first study on dark-field chest radiographs of human bodies showed that the dark-field signal could be reliable quantified [55].…”

In-vivo X-ray dark-field computed tomography for the detection of radiation-induced lung damage in mice

“…Further details can be found in Ref. [16] . The left lung was not irradiated and used as a reference for healthy tissue.…”

“…Tomographic images were taken at the beginning of the study (before irradiation) and 16 weeks after irradiation. This point in time was selected because an earlier evaluation [16] showed that first manifestations of lung damage are detectable at this point in time, while the sensitivity of both contrast types is still expected to be below 100%. At the beginning, the experiment comprised a control group and an irradiated group of six mice each, but 16 weeks post irradiation one mouse of the control group is missing due to premature death.…”

“…This makes dark-field imaging particularly suited for lung imaging, as this type of scattering appears on multiple microscopic air-tissue interfaces present there. Its application for the detection of lung disorders provided interesting results for inflammation [14] , fibrosis [15] , [16] , emphysema [17] , [18] , [19] , [20] and tumours [21] . Investigating its benefits for the detection of lung damages caused by radiotherapy has only started [16] .…”

“…Its application for the detection of lung disorders provided interesting results for inflammation [14] , fibrosis [15] , [16] , emphysema [17] , [18] , [19] , [20] and tumours [21] . Investigating its benefits for the detection of lung damages caused by radiotherapy has only started [16] . While these previous studies focussed on dark-field radiography, it is expected that dark-field tomography can provide enhanced image quality and additional information compared to radiography due to its three-dimensional nature without superimposed image features.…”