Phase-contrast X-ray tomography resolves the terminal bronchioles in free-breathing mice

Abstract Phase-contrast X-ray lung imaging has broken new ground in preclinical respiratory research by improving contrast at air/tissue interfaces. To minimize blur from respiratory motion, intubation and mechanical ventilation is commonly employed for end-inspiration gated imaging at synchrotrons and in the laboratory. Inevitably, the prospect of ventilation induced lung injury (VILI) renders mechanical ventilation a confounding factor in respiratory studies of animal models. Here we demonstrate proof-of-principle 3D imaging of the tracheobronchial tree in free-breathing mice without mechanical ventilation at radiation levels compatible with longitudinal studies. We use a prospective gating approach for end-expiration propagation-based phase-contrast X-ray imaging where the natural breathing of the mouse dictates the acquisition flow. We achieve intrapulmonary spatial resolution in the 30-μm-range, sufficient for resolving terminal bronchioles in the 60-μm-range distinguished from the surrounding lung parenchyma. These results should enable non-invasive longitudinal studies of native state murine airways for translational lung disease research in the laboratory.

Abstract Phase-contrast X-ray lung imaging has broken new ground in preclinical respiratory research by improving contrast at air/tissue interfaces. To minimize blur from respiratory motion, intubation and mechanical ventilation is commonly employed for end-inspiration gated imaging at synchrotrons and in the laboratory. Inevitably, the prospect of ventilation induced lung injury (VILI) renders mechanical ventilation a confounding factor in respiratory studies of animal models. Here we demonstrate proof-of-principle 3D imaging of the tracheobronchial tree in free-breathing mice without mechanical ventilation at radiation levels compatible with longitudinal studies. We use a prospective gating approach for end-expiration propagation-based phase-contrast X-ray imaging where the natural breathing of the mouse dictates the acquisition flow. We achieve intrapulmonary spatial resolution in the 30-μm-range, sufficient for resolving terminal bronchioles in the 60-μm-range distinguished from the surrounding lung parenchyma. These results should enable non-invasive longitudinal studies of native state murine airways for translational lung disease research in the laboratory.