Feasibility of quantification of murine radiation-induced pulmonary fibrosis with microCT imaging

Abstract

Mouse models of radiation-induced pulmonary fibrosis (RIPF) are commonly produced to find novel treatments for the condition. However, current models are not always assesed in a clinically-relevant manner. Clinics diagnose and track RIPF through CT scanning rather than observing time-to-death. An established timeline of RIPF lesion development in a murine model is therefore needed. Male C57Bl/6 mice (n=43) were irradiated with a single dose of 20 Gy to the whole thoracic area delivered by an 320 kV X-Rad cabinet irradiator. CT was performed with respitory gating at two week time points and developed images to identify RIPF pathology in vivo. Confirmation of CT findings was performed via histology on the lungs using Mason’s trichrome staining. CT images were segmented to quantify fibrosis and lung which are then summed to give total volume. The fibrotic fraction was calculated upto 26 weeks. Significant increases in fibrotic fraction compared to the baseline microCT scans for each individual mouse acquired prior to the 20 Gy exposure are seen beginning at 10–12 weeks. Tidal lung volume was also calculated by subtracting expiration scan volumes from inspiration scan volumes. However the decrease in tidal lung volume over time was not statisitically significant. Computed tomography (CT) imaging was used to quantify the increase in fibrosis over time in our mouse model. However, the results were highly variable among individual mice after irradiation. CT imaging should be used in future studies looking at treatments for RIPF as it allows for measuring the extent of pathology non-invasively in a clinically-relevant manner.