Abstract

ObjectiveAssessing 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.MethodsTwo 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.ResultsRadiation-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.ConclusionX-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.

Highlights

  • Radiotherapy is a common treatment method for thoracic tumors that can come along with severe side effects for the lung, such as inflammation, fibrosis, or even cancer [1]

  • Summary statement This research shows that an advantage in time is gained when using x-ray dark-field radiography instead of x-ray transmission radiography for the detection of radiation-induced lung damage

  • It showed a thickening of the alveolar walls in the affected area of the irradiated right lung, proving the occurrence of fibrosis

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Summary

Introduction

Radiotherapy is a common treatment method for thoracic tumors that can come along with severe side effects for the lung, such as inflammation, fibrosis, or even cancer [1]. In small-animal radiotherapy research, radiationinduced lung damage, emphysema [2,3,4,5], fibrosis [6,7,8,9,10,11], and imaging dose [12,13,14,15,16] have been investigated. Radiographic x-ray dark-field imaging requires less dose than CT and has delivered promising results for the detection of inflammation [22], fibrosis [23], emphysema [24,25,26,27], and tumors [28] in mice. We investigated the combination of smallanimal radiotherapy and radiography in a pre-clinical murine study determining a possible advantage of x-ray darkfield contrast over x-ray transmission contrast for the detection of developing radiation-induced lung damage

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