With the emergence of innovative interventions in lung disease both at early and end stages of the disease (i.e.: retinoid therapy or lung volume reduction surgery for emphysema and receptor blocking therapies for lung cancer), it has become clear that sensitive, objective, accurate and repeatable measures must be developed to determine presence and regional distribution of lung abnormalities. Standard pulmonary function tests are inadequate for the task. While x-ray CT has been accepted as the most likely single modality providing a comprehensive regional lung assessment, visual scoring of the radiographs have proven to be inadequate, given the requirements of objectivity, repeatability and sensitivity. As helical scanners emerge with the ability of acquiring multi-slice data sets in less than a heart beat, the possibilities of assessing both structure and function simultaneously further limits the utility of a visual image assessment. We propose a Bioengineering Research Partnership, bring together a team of Engineers, Scientists, and Physicians from 6 academic institutions to collaborate in developing the technologies which will allow for the use of dynamic, volumetric x-ray CT to assess the lung. At the core of the research program will be a state-of-the-art helical CT facility that will evolve over the course of the proposal towards true dynamic volumetric imaging capabilities. We propose to develop a model of the normal human lung for three decades of adult age. This model will consist of an atlas of the normal anatomy down to the sub-lobar segments. Attached to these sub-lobar segments will be parameters of the normal range and distribution of airway, blood vessel, tissue, blood flow, and ventilation properties assessed at two standardized airway pressures. In addition, this model will provide normal ranges for image-based measures of chest wall mechanics and their coupling with regional lung compliance. Also attached to the model will be global parameters (PFT's, Broncho- Alveolar Lavage, exhaled Nitric Oxide). To assess the accuracy of such an approach, we focus on smoking related lung disease: specifically emphysema and cancers with assessment focused both in patients with known disease as well as in a comparison of nonsmokers and smokers with normal pulmonary function tests. The accuracy of the individual measures to be developed under this proposal will be verified in normal animals using both isolated and in-vivo lungs and using a dog model of emphysema. We hypothesize that such a comprehensive model, based upon measurements from non- invasive, dynamic, volumetric imaging can be built for the human lung and applied to the early, preclinical assessment of lung abnormality.
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