DOI

10.17077/etd.vlz0jkqp

Document Type

Dissertation

Date of Degree

Fall 2016

Degree Name

PhD (Doctor of Philosophy)

Degree In

Biomedical Engineering

First Advisor

Joseph M. Reinhardt

First Committee Member

Eric A Hoffman

Second Committee Member

John D Newell Jr.

Third Committee Member

Jessica C Sieren

Fourth Committee Member

David W Kaczka

Fifth Committee Member

Surya P Bhatt

Abstract

Chronic obstructive pulmonary disease (COPD) is a growing health concern associated with high morbidity and mortality, and is currently the third-ranked cause of death in the United States. COPD is characterized by airflow limitation that is not fully reversible and includes chronic bronchitis, functional small airway disease, and emphysema. The interrelationship between emphysema and airway disease in COPD makes it a highly complex and heterogeneous disorder. Appropriate diagnosis of COPD is vital to administer targeted therapy strategies that can improve patient’s quality of life and reduce the frequency of COPD associated exacerbations. Although spirometry or pulmonary function tests are currently the gold standard for the diagnosis and staging of the disease, their lack of reproducibility and minimal information on regional characterization of the lung tissue destruction makes it hard to rely on to phenotype COPD population and predict disease progression. Quantification of COPD, as done by computed tomography (CT) methods has seen significant advancements, helping us understand the complex pathophysiology of this disease. The prospective and established techniques that are derived from CT imaging such as densitometry, texture, airway, and pulmonary vasculature-based analyses have been successful in regional characterization of emphysema related lung tissue destruction and airway disease related morphological changes in COPD patients. Although, these measures enriched our diagnostic and treating capability of COPD, they lack information on patient specific alterations in lung mechanics and regional parenchymal stresses. This valuable information can be achieved through the use of image registration protocols. Our main goal of this research work is to examine and evaluate the role of lung mechanical measures derived from CT image registration techniques in COPD diagnosis, phenotyping, and progression.

Public Abstract

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the United States. COPD is a characterized by progressive airflow limitation and is associated with increasing mortality and morbidity. COPD is often used as an umbrella term for multiple disease components: tissue destruction due to emphysema, airway remodeling and narrowing due to small and large airway disease. The complex admixture of individual disease components in COPD makes it a highly heterogeneous disorder. The current gold standard of COPD diagnosis is by quantifying airflow obstruction using spirometry. However, spirometry is a global measure and is not helpful in assessing the contribution of emphysema and airway disease separately in COPD patients. Computed tomography (CT) is increasingly being used to characterize and quantify the lung tissue of COPD patients. The vast majority of CT image-based research of COPD is based on the density and the texture analysis of either inspiratory or expiratory CT images, thus providing the regional characterization of the disease. In this thesis, we used the information derived from both inspiratory and expiratory CT to capture mechanical properties of lung tissue in COPD patients. We further explored the role of the CT-derived lung mechanics in COPD presence and severity, and disease progression.

Keywords

COPD, CT, IMAGING, LUNG MECHANICS, PROGRESSION

Pages

xiii, 143 pages

Bibliography

Includes bibliographical references (pages 123-143).

Copyright

Copyright © 2016 Sandeep Bodduluri

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