Three-dimensional computed tomography imaging in an animal model of emphysema

Abstract

Emphysema is a major health problem and novel drugs are needed. Animal disease models are pivotal in their development, but the validity and sensitivity of current tools for the evaluation of drug efficacy is limited. The usefulness of micro computed tomography (CT) as an innovative tool to assess emphysema in a mouse model was investigated.Serial CT scans were performed in bi-weekly intervals in Smad3 knockout (KO) mice, which spontaneously develop airspace enlargement. Lung density was quantified in two-and threedimensional images and correlated to mean linear intercept and lung compliance.CT scans of Smad3 KO lungs revealed a significant decrease in lung density at age 8 weeks and a further progression at age 14 weeks with respect to age-matched wild-type (WT) animals. Emphysema could be reliably assessed with both the two-and three-dimensional approach, but the three-dimensional approach was superior, due to normalisation to lung volumes and less variability. Lung compliance by week 14 was 0.053¡0.005 and 0.034¡0.002% of maximum volume?cmH 2 O -1 for KO and WT mice, respectively, reflecting significant physiologically relevant emphysema. Small animal computed tomography imaging and density quantification in a reconstructed three-dimensional image is a useful tool for quantifying emphysematous changes in an animal disease model. It adds significant information to conventional assessment.

Evaluation of allergic lung inflammation by computed tomography in a rat model in vivo

“…Methodological differences could be minimised by employing standardisation techniques, thus allowing for inter-study comparisons. For example, CT histogram data can be standardised by expressing bin volumes as the percentage of total volume, as shown by FROESE et al [2], and, furthermore, by subtracting baseline values for each animal. As demonstrated in figure 1, the results obtained by Methods 1 and 2 were extremely similar in nature once the suggested standardisation methodologies were applied.…”

“…Two methods of volume segmentation, as described by others [1][2][3][4]13], were performed, in order to assess the advantages of and similarities between these methods. In Method 1, the thoracic volume was segmented by defining a region of interest that encapsulated the entire lung by manually outlining the ribcage and chest wall using characteristic landmarks and interpolation.…”

“…Its usefulness relies on the ability to anatomically and functionally measure processes in the lung across an experimental protocol. Progress has already been made using this imaging modality in studies of fibrosis and emphysema [1][2][3]. With respect to asthma, research utilising CT immediately following sacrifice, i.e.…”

Airway segmentation and analysis for the study of mouse models of lung disease using micro-CT

“…Compared to the control group, emphysematous mice show considerably darker lungs, due to the loss of parenchymal tissue (Froese et al 2007). This, together with a stronger tendency to movement-related artifacts, leads to poor intensity contrast between airways and parenchyma.…”

“…This technology has been successfully used to study different disease models such as lung cancer and emphysema (De Clerck et al 2004, Postnov et al 2005, Froese et al 2007. Furthermore, its applications are likely to grow with the advent and improvement of flat-panel detectors.…”