Dual energy CT based approach to assessing early pulmonary vascular dysfunction in smoking-associated inflammatory lung disease

CT is a powerful method for noninvasive assessment of the lung. Advancements to CT technology have guided the high-resolution structural and functional assessment of lung diseases. This has helped make the transition from characterizing the severity of lung disease to novel phenotyping of disease subtypes. Chronic obstructive pulmonary disease (COPD) is a spectrum of inflammatory lung disease affecting lung parenchyma, airways, and the pulmonary and systemic vasculature. Quantitative CT-based measures have largely focused on quantifying the extent of airway and parenchymal damage with disease. Recently perfusion CT method has been used to assess the pulmonary vascular bed. This technique was used to demonstrate a vascular etiology of smoking-associated centriacinar emphysema (CAE), a subtype of the COPD spectrum. However, technical challenges have limited the transition of this CT method to clinical studies to assess pulmonary vascular physiology. In this thesis, we introduce dual energy CT-perfused blood volume (DECT-PBV) as a novel image-based biomarker to assess peripheral pulmonary vascular dysfunction. Using this technique, we show that smoking-associated pulmonary perfusion heterogeneity, a marker of abnormal blood flow is a reversible process, in the midst of smoking-associated lung inflammation, and not a product of advanced lung disease. We demonstrate, via regional PBV measures and structural measures of the central pulmonary vessels, that the reversibility of pulmonary perfusion heterogeneity is a direct result of increased peripheral (downstream) parenchymal perfusion. We validate our quantitative imaging approach in a unique cohort of early CAE-susceptible smokers using a pharmaceutical intervention to dilate the pulmonary parenchymal vascular bed. The validated DECT approach and our novel DECT imaging findings extend our characterization of the vascular phenotype in inflammatory lung disease and provide a framework for future quantitative imaging studies of the lung to assess early intervention targeted to pulmonary vessels.