Imaging in animal models: bridging experimental findings and human pathophysiology

Abstract

Acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis are major respiratory conditions associated with significant morbidity and, in some cases, high mortality. A variety of animals models have been established to study these disorders, primarily focusing on histologic alterations, cellular signalling pathways, inflammatory responses, lung perfusion, gas-exchange abnormalities, and response to emerging therapies. Imaging techniques play a crucial role in these investigations, enabling in vivo assessment of lung structure and function. The most widely used imaging modalities include computed tomography (CT), positron emission tomography (PET), and electrical impedance tomography (EIT). While CT and, to a variable extent, PET involve ionizing radiation, EIT is a radiation-free technique. Despite anatomical differences between species, many imaging and physiological findings observed in animal models are consistent with those seen in critically ill patients, enhancing their translational relevance. This narrative review provides a comprehensive overview of the applicability of these imaging techniques in animal models and explores their relevance to human pathophysiology and clinical management.

Keywords: Animal models; Computed tomography; Electrical impedance tomography; Imaging; Lung perfusion; Ventilation.

Fig. 1

Video microscopy and OCT of subpleural alveoli in rat in vivo. First row: healthy tissue during mechanical ventilation in the supine position. The alveoli are homogeneously distributed and have a honeycomb-like arrangement. Second row: diseased tissue in a TWEEN-20 induced ARDS model. Due to the absence of surfactant, the alveoli in the middle image area are filled with protein-rich liquid, which can be distinguished in the OCT images. The surrounding alveoli are overinflated (nearly round) with interstitial edema in between, although the same ventilation settings were selected as in the healthy state shown in the first row. The images show that there is no alveolar collapse in ARDS, but liquid filling and therefore reduced compliance and maybe ventilator-induced lung injury. Note the different scale bars in images of healthy and diseased tissue

Fig. 2

Porcine pancreatic elastase (PPE) exposure induces lung damage with an extensive emphysematous area in the experimental model of COPD. C57BL/6 mice were instilled with porcine pancreatic elastase, and 28 days later, micro-CT analysis was performed on the Quantum GX2 equipment. The representative CT image was obtained from an animal in the supine position at the end of expiration, with the following parameters: 4 min scanning time over a whole angle of 360°, 70 kV, and 114 µA. Control animal representative image (A) and porcine pancreatic elastase-instilled animal representative image (B). Note how the lung of the elastase-instilled animal appears darker than the control lung

Fig. 3

Video microscopy and OCT imaging of mouse trachea. A 1300-nm OCT system was used to visualize the trachea in vivo. Due to scattering and cartilage structures, the penetration depth is limited. Here, fiber-coupled and endoscopic systems have a particular advantage in imaging the entire lumen of the trachea. Nevertheless, the microstructure of the trachea can be clearly recognized and structural changes in the airways in asthma and chronic diseases can be examined in detail. dm digastricus muscle, gt gland tissue, tc tracheal cartilage, tm trachealis muscle

Fig. 4

Inhalation of silica particles induces the formation of lung granuloma in an experimental model of silicosis. Swiss-Webster mice were exposed to silica particles and were analyzed 28 days after the instillation. Micro-CT scans were performed on a Quantum GX2 scanner. The representative CT image was obtained from an animal in the supine position at the end of expiration, with the following parameters: 4 min scanning time over a whole angle of 360°, 70 kV, and 114 µA. Healthy animal representative image (A) and silica-instilled animal representative image (B). The arrow points to the area with diffuse consolidations