Micro-CT-derived ventilation biomarkers for the longitudinal assessment of pathology and response to therapy in a mouse model of lung fibrosis

Abstract

Experimental in-vivo animal models are key tools to investigate the pathogenesis of lung disease and to discover new therapeutics. Histopathological and biochemical investigations of explanted lung tissue are currently considered the gold standard, but they provide space-localized information and are not amenable to longitudinal studies in individual animals. Here, we present an imaging procedure that uses micro-CT to extract morpho-functional indicators of lung pathology in a murine model of lung fibrosis. We quantified the decrease of lung ventilation and measured the antifibrotic effect of Nintedanib. A robust structure-function relationship was revealed by cumulative data correlating micro-CT with histomorphometric endpoints. The results highlight the potential of in-vivo micro-CT biomarkers as novel tools to monitor the progression of inflammatory and fibrotic lung disease and to shed light on the mechanism of action of candidate drugs. Our platform is also expected to streamline translation from preclinical studies to human patients.