Quantification of regional ventilation-perfusion ratios with PET

The topographic matching of alveolar ventilation (V̇_A) and perfusion (Q̇) is the main determinant of gas exchange efficiency of the lung. However, no pulmonary functional imaging technique has been shown to predict whole-lung gas exchange in health and disease. This study aims to present a PET-based method to estimate regional alveolar ventilation-to- perfusion ratios (V̇_A/Q̇) predictive of arterial blood gases. Methods: The method is based on the regional tracer kinetics of ¹³N-nitrogen (¹³NN) after an intravenous bolus injection during a breath-hold period and subsequent washout from the lungs with resumption of breathing. The method takes into account the presence of inter- and intraregional nonuniformities at length scales smaller than the imaging spatial resolution. An algorithm used regional tracer washout to classify regional V̇_A/Q̇ uniformity. Intraregional V̇_A/Q̇ mismatch in nonuniform regions was described with a 2-compartment model. Regional V̇_A/Q̇ estimates were combined into a whole-lung distribution of V̇_A/Q̇ ratios and were used to compute global arterial blood gases. The method was applied to 3-dimensional PET data from anesthetized and mechanically ventilated sheep before and after methacholine bronchoconstriction (n = 3) and pulmonary embolism (n = 3) and after saline lung lavage (n = 3). Results: PET images revealed regional changes in ventilation and perfusion consistent with the different disease models. Quantification of the images using PET-derived V̇_A/Q̇ distributions showed unimodal and narrow distributions in control conditions that became wider and unimodal after pulmonary embolism and saline lung lavage and bimodal after bronchoconstriction. Images of regional gas exchange allowed for visualization of regional gas exchange. Arterial blood gases estimated from the PET-based V̇_A/Q̇ distributions closely agreed with measured values (partial pressure of oxygen, arterial [PaO₂]: r ² = 0.97, P < 0.001; partial pressure of carbon dioxide, arterial [PacO₂]: r² = 0.96, P < 0.001). Conclusion: Tracer kinetics analysis of PET images after an intravenous injection of ¹³NN provides a quantitative assessment of regional V̇_A/Q̇ heterogeneity including that corresponding to length scales smaller than the spatial resolution of the imaging method. Quantification of V̇_A/Q̇ mismatch obtained with the presented technique is directly related to severity of gas exchange impairment as determined by arterial blood gases.