UC San Diego

Gas exchange between inhaled alveolar air and pulmonary capillary blood occurs in the lung. The relationship between ventilation and perfusion determines the global efficiency of gas exchange in the lung. The normal healthy lung maintains a regional ventilation-perfusion ratio close to unity, whereas in disease, the regional ventilation-perfusion mismatch results in inefficient gas exchange, leading to arterial hypoxemia. The original research presented in this dissertation focused on factors effecting on the regional distribution of pulmonary perfusion in supine humans, namely the effects of (1) hypoxic pulmonary vasoconstriction (HPV), and (2) lung tissue stretch due to tidal volume lung inflation. The work performed required an understanding of pulmonary physiology, biomechanics, functional magnetic resonance imaging (MRI) and image processing. An arterial spin labeling MR sequence, combined with pulmonary proton density imaging, was used to quantify the spatial distribution of pulmonary perfusion. The alterations in the distribution of pulmonary perfusion were induced by (1) inhalation of gases of different oxygen concentration, and (2) tidal volume lung inflation. The tidal volume lung inflation study involved MR lung images obtained at different lung volumes. A deformable image registration technique, using a piecewise polynomial interpolation method, was developed to warp acquired pulmonary perfusion images into the shape of a reference lung volume such that lung images were compared based on corresponding anatomy. The main results of this work were : (1) mild global hypoxia and hyperoxia, induced by the inhalation of different fraction of inspired oxygen gas mixtures (FIO₂ = 0.125 and 0.3, respectively) do not result in changes in the heterogeneity or redistribution of pulmonary perfusion, indicating that hypoxic pulmonary vasoconstriction is not the major contributor affecting pulmonary perfusion heterogeneity in the normal supine human lung. (2) Tidal volume lung inflation did not cause significant changes in the spatial distribution of pulmonary perfusion; however, the fractional distribution of pulmonary perfusion was redistributed away from the nondependent region of lung at the higher lung volume, indicating that the changes in the gravitational height of the lung, which result in changes in hydrostatic pressure distribution likely contribute more significantly than the overall changes in pulmonary vasculare resistance induced by lung tissue stretch