In Vivo Quantitative Assessment of Myocardial Structure, Function, Perfusion and Viability Using Cardiac Micro-computed Tomography

The use of Micro-Computed Tomography (MicroCT) for in vivo studies of small animals as models of human disease has risen tremendously due to the fact that MicroCT provides quantitative high-resolution three-dimensional (3D) anatomical data non-destructively and longitudinally. Most importantly, with the development of a novel preclinical iodinated contrast agent called eXIA160, functional and metabolic assessment of the heart became possible. However, prior to the advent of commercial MicroCT scanners equipped with X-ray flat-panel detector technology and easy-to-use cardio-respiratory gating, preclinical studies of cardiovascular disease (CVD) in small animals required a MicroCT technologist with advanced skills, and thus were impractical for widespread implementation. The goal of this work is to provide a practical guide to the use of the high-speed Quantum FX MicroCT system for comprehensive determination of myocardial global and regional function along with assessment of myocardial perfusion, metabolism and viability in healthy mice and in a cardiac ischemia mouse model induced by permanent occlusion of the left anterior descending coronary artery (LAD)

Multiphase micro-computed tomography reconstructions provide dynamic respiratory function in a mouse lung fibrosis model

Summary: Micro-computed tomography derived functional biomarkers used in lung disease research can significantly complement end-stage histomorphometric measures while also allowing for longitudinal studies. However, no approach for visualizing lung dynamics across a full respiratory cycle has yet been described.Using bleomycin-induced lung fibrosis and the antifibrotic drug nintedanib as a test model, we implemented a four-dimensional (4D) micro-CT imaging approach consisting of 30 reconstructed volumes per respiratory cycle, coupled with deep-learning-assisted segmentation of lung volumes. 4D micro-CT provided an accurate description of inhalatory and exhalatory lung dynamics under resting conditions and revealed an inflammation-related obstructive pattern at day 7, followed by a restrictive pattern associated with fibrosis development at day 21. A milder restriction and fibrotic pathology resulted from nintedanib treatment. The similarity of 4D micro-CT data with those produced by diagnostic measurements, also points to its great potential as an exploratory tool for the discovery of clinically relevant therapeutic compounds

Longitudinal assessment of bleomycin-induced lung fibrosis by Micro-CT correlates with histological evaluation in mice

Background: The intratracheal instillation of bleomycin in mice induces early damage to alveolar epithelial cells and development of inflammation followed by fibrotic tissue changes and represents the most widely used model of pulmonary fibrosis to investigate human IPF. Histopathology is the gold standard for assessing lung fibrosis in rodents, however it precludes repeated and longitudinal measurements of disease progression and does not provide information on spatial and temporal distribution of tissue damage. Here we investigated the use of the Micro-CT technique to allow the evaluation of disease onset and progression at different time-points in the mouse bleomycin model of lung fibrosis. Micro-CT was throughout coupled with histological analysis for the validation of the imaging results. Methods: In bleomycin-instilled and control mice, airways and lung morphology changes were assessed and reconstructed at baseline, 7, 14 and 21 days post-treatment based on Micro-CT images. Ashcroft score, percentage of collagen content and percentage of alveolar air area were detected on lung slides processed by histology and subsequently compared with Micro-CT parameters. Results: Extent (%) of fibrosis measured by Micro-CT correlated with Ashcroft score, the percentage of collagen content and the percentage of alveolar air area (r 2 = 0.91; 0.77; 0.94, respectively). Distal airway radius also correlated with the Ashcroft score, the collagen content and alveolar air area percentage (r 2 = 0.89; 0.78; 0.98, respectively). Conclusions: Micro-CT data were in good agreement with histological read-outs as micro-CT was able to quantify effectively and non-invasively disease progression longitudinally and to reduce the variability and number of animals used to assess the damage. This suggests that this technique is a powerful tool for understanding experimental pulmonary fibrosis and that its use could translate into a more efficient drug discovery process, also helping to fill the gap between preclinical setting and clinical practice

Longitudinal assessment of bleomycin-induced lung fibrosis by Micro-CT correlates with histological evaluation in mice

Background: The intratracheal instillation of bleomycin in mice induces early damage to alveolar epithelial cells and development of inflammati