AbstractBackgroundPulmonary emphysema is a part of chronic obstructive pulmonary disease, which is an irreversible chronic respiratory disease. In order to avoid further damage to lung tissue, early diagnosis and treatment of pulmonary emphysema is essential.PurposeEarly pulmonary emphysema diagnosis is difficult with conventional radiographic imaging. Recently, x‐ray phase contrast imaging has proved to be an effective and promising imaging strategy for soft tissue, due to its high sensitivity and multi‐contrast. The aim of this study is to diagnose pulmonary emphysema early utilizing an x‐ray Talbot‐Lau interferometer (TLI).MethodsWe successfully established the mouse model of emphysema by porcine pancreatic elastase treatment, and then used the established x‐ray TLI to perform imaging experiments on the mice with different treatment time. The traditional absorption CT and phase contrast CT were obtained simultaneously through TLI. The CT results and histopathology of mice lung in different treatment time were quantitatively analyzed.ResultsBy imaging mice lungs, it can be found that phase contrast has higher sensitivity than absorption contrast in early pulmonary emphysema. The results show that the phase contrast signal could distinguish the pulmonary emphysema earlier than the conventional attenuation signal, which can be consistent with histological images. Through the quantitative analysis of pathological section and phase contrast CT, it can be found that there is a strong linear correlation.ConclusionsIn this study, we quantitatively analyze mean linear intercept of histological sections and CT values of mice. The results show that the phase contrast signal has higher imaging sensitivity than the attenuation signal. X‐ray TLI multi‐contrast imaging is proved as a potential diagnostic method for early pulmonary emphysema in mice.