Document Type

Dissertation

Date of Degree

Spring 2010

Degree Name

PhD (Doctor of Philosophy)

Degree In

Biomedical Engineering

First Advisor

Eric Hoffman

Abstract

Emphysema, a subset of COPD, occurs due to an abnormal inflammatory response to noxious gases or particles leading an influx of immunologic cells. Recent studies have demonstrated endothelial dysfunction in COPD subjects and are suggestive of a vascular phenotype present in COPD that is not fully characterized. We hypothesize that processes affecting the pulmonary vasculature lead to early changes important in the pathogenesis of COPD. This work focuses on the use of multidetector-row computed tomography (MDCT)-based measures of pulmonary blood flow (PBF), mean transit time (MTT) and pulmonary vascular volume (TPVV) to gain new insights into vasculature-related changes present in COPD. As a precursor to using perfusion MDCT imaging to phenotype lung disease, we demonstrated good regional correlation of PBF measurements obtained with MDCT imaging and fluorescent microspheres (FMS) at a FMS piece size resolution of 1.9 cm3 and regional volume level of 8-10 cm3. Additionally, we developed an ex vivo perfusion system, and applied quantitative image analysis techniques to study the lung preparation's stability over 120 minutes. We further validated CT-based PBF and MTT measurements by demonstrating physiologically appropriate responses to a range of flow rates with this new system. Finally, quantitative MDCT-based measurements were used to characterize a novel phenotype of emphysema and test hypotheses regarding vasculature-related changes in smokers and COPD subjects. We demonstrated increased heterogeneity in regional MTT and PBF measurements in smokers with preclinical emphysema compared with smokers with normal lung function and imaging studies and nonsmokers. This data is supportive of the notion that inflammatory-based vascular responses to hypoxia are occurring in smokers susceptible to COPD, but are successfully blocked in smokers without signs of emphysema. A new CT-based measure, TPVV, was studied and we demonstrate its association with total lung volume and body size metrics. TPVV measurements correlated with measures of COPD severity. A trend linking increased TPVV with increased endothelial dysfunction was observed, suggesting that pathological changes of COPD have an effect on the pulmonary vasculature. This work demonstrates the importance of functional information that can compliment structural, anatomical information to answer questions based on the lung physiology and pathological disease processes.

Keywords

COPD, CT, Emphysema, Perfusion, Pulmonary Blood Flow

Pages

xv, 156 pages

Bibliography

Includes bibliographical references (pages 140-156).

Copyright

Copyright 2010 Sara Alford

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