Abstract
The aim of this study was to evaluate the feasibility of early stage imaging of acute lung inflammation in mice using grating-based X-ray dark-field imaging in vivo. Acute lung inflammation was induced in mice by orotracheal instillation of porcine pancreatic elastase. Control mice received orotracheal instillation of PBS. Mice were imaged immediately before and 1 day after the application of elastase or PBS to assess acute changes in pulmonary structure due to lung inflammation. Subsequently, 6 mice from each group were sacrificed and their lungs were lavaged and explanted for histological analysis. A further 7, 14 and 21 days later the remaining mice were imaged again. All images were acquired with a prototype grating-based small-animal scanner to generate dark-field and transmission radiographs. Lavage confirmed that mice in the experimental group had developed acute lung inflammation one day after administration of elastase. Acute lung inflammation was visible as a striking decrease in signal intensity of the pulmonary parenchyma on dark-field images at day 1. Quantitative analysis confirmed that dark-field signal intensity at day 1 was significantly lower than signal intensities measured at the remaining timepoints, confirming that acute lung inflammation can be depicted in vivo with dark-field radiography.
Highlights
Acute lung inflammation is characterized by decreased endothelial cell barrier function, increased vascular permeability and influx of neutrophils leading to the development of acute bilateral, pulmonary infiltrates, followed by impaired oxygenation[1]
As an additional sign of lung injury, lavages in the experimental group showed a reddish color, typical for fluid enriched with erythrocytes, compared to a clear appearance of lavages in the control group. 21 days after application of elastase the number of leucocytes had returned to baseline (3.9 × 104 ± 1.4 × 104; p = 0.1 compared to control group at day 21), indicating that the acute inflammatory reaction had stopped
Representative examples of haematoxylin and eosin (H&E) stained sections from control lungs and lungs surgically extracted 1 and 21 days after application of elastase are presented in Fig. 2A and B
Summary
Acute lung inflammation is characterized by decreased endothelial cell barrier function, increased vascular permeability and influx of neutrophils leading to the development of acute bilateral, pulmonary infiltrates, followed by impaired oxygenation[1]. Chest radiography is still the most frequently used radiological tool to diagnose and monitor lung inflammation[6] Radiographic findings, such as bilateral lung opacities, that can either appear diffuse, patchy or homogenous, reflect interstitial or alveolar edema[7,8,9]. As these signs are nonspecific and can occur in different kinds of pulmonary edema (e.g. due to heart failure), high interobserver variability is found in chest radiograph-based diagnosis of acute lung inflammation[10]. Phase-contrast images visualize the phase-shift of X-ray beams within tissue with enhanced representation of edges, making large airways such as the trachea or main bronchi visible[13,14,15]
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