ENGINEERING IN MEDICINE COLLOQUIUM
TITLE: Quantitative PET Imaging of Ventilator-Induced Lung Injury
Tyler Wellman, Ph.D.
In this seminar, I will present positron emission tomography (PET) imaging approaches for quantification of regional lung strain, ventilation, and perfusion in mechanically ventilated lungs. Mechanical ventilation is a life-saving intervention in patients with respiratory failure, but can also produce inflammation in the lungs through cyclic tissue strain. While it is known that high tidal volumes can cause inflammation in small animals, it remains unclear how inflammation develops in large, heterogeneously expanding lungs. We hypothesized that in heterogeneous lungs comparable in size to humans, regional inflammatory activation is directly related to both the magnitude and heterogeneity of tidal strain. The goal of this work was to develop quantitative PET imaging techniques to test this hypothesis in sheep models of ventilator-induced lung injury.
First, we developed an approach to measure regional tidal lung strain using respiratory-gated PET of inhaled 13N-nitrogen (13NN). Second, we advanced PET techniques for quantification of ventilation heterogeneity underlying the PET resolution, and implemented a new length-scale analysis of ventilation heterogeneity. Third, we came up with a tracer kinetic model of pulmonary 18F-FDG kinetics that allows for estimation of regional lung perfusion. Finally, we combined these PET techniques with dynamic 18F-FDG-PET measurements of lung metabolism, an indicator of inflammation during lung injury, to study the relationships between regional lung strain and inflammation in sheep mechanically ventilated with and without intravenous lipopolysaccharide (LPS) infusion. We found linear relationships between regional strain and metabolism, with a significant increase in slope resulting from exposure to LPS, indicating synergy between strain and LPS in amplifying lung inflammation. Protective ventilation reduced peak inflammation by homogenizing and decreasing regional lung strain. These results have important implications for the rational design of mechanical ventilation protocols aimed at preventing lung injury.
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