| Summary: | Lung cancer and chronic obstructive pulmonary disease (COPD) are among
the deadliest diseases worldwide, and animal models play a key role in
understanding the natural history of these diseases, as well as in pre-clinical
treatment trials. Different techniques can be used to study animal models
of lung disease, such as pulmonary function tests or histology. X-ray microcomputed
tomography (micro-CT) represents a very convenient technology
to obtain three-dimensional images of the lungs with minimum invasiveness.
Multiple preliminary studies have shown the use of micro-CT to assess
the progress of mouse models of lung disease. In this thesis, we set up a
generic protocol for image acquisition which is of use even for heavily diseased
animals. The protocol includes endotracheal intubation, pulmonary
function tests and iso-pressure breath holds for movement artifact reduction.
Chest micro-CT image segmentation and analysis methods have been
developed to quantify the effects of disease. These methods allow for quantitative
measurements on the lungs and the airways separately, which can be
used to monitor disease development. Moreover, significant contributions
have been made to the field of atlas-based segmentation, with applications
in multiple image modalities and segmentation problems.
Developed methods have been applied to characterize the dynamic evolution
of three relevant mouse models of lung disease: elastase-induced
emphysema, silica-induced chronic pulmonary inflammation and urethaneinduced
lung cancer combined with emphysema. Apart from micro-CT,
other techniques have also been used to complement the data.
Results show the use of micro-CT and automated image analysis to
quantify the effect of different pulmonary diseases on small animal models.
Methods presented in this thesis will be of use to characterize other models
of lung disease, as well as for treatment testing.
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