Quantification of Pulmonary Physiological Parameters for use with Positron Emission Tomography

Knowledge of the dead space breathing volume is important in order to insure that mechanical ventilation is sufficient and to standardize experimental conditions. Measurement of the dead space at various time points within an experimental protocol provides useful information in elucidating the meaning and possibly the cause of other physiologic changes. Therefore, a system has been developed to measure the dead space volume in real-time for mechanically ventilated subjects. Calculations were made using an algebraic implementation of Fowler's method on identified exhalations of measured capnographic curves. The system was successfully utilized on two intubated, mechanically ventilated sheep, and advantages and limitations were discussed. Regional pulmonary parameters have been analyzed using positron emission tomography (PET) studies in which an IV bolus injection of "NN in saline is given at the onset of a period of apnea. However, low alveolar gas-volume to perfusion ratios complicate the analysis because such regions cause a greater amount of 1 3 NN to be reabsorbed from alveolar spaces by the bloodstream following the passage of the initial bolus. Because of these complications in analyzing the PET images directly, two mathematical models of the tracer kinetics measured in the lungs by the PET camera and in the systemic arteries by a peripheral gamma-counter were developed. The models were based on first-order differential equations describing the behavior of a shunting lung unit representing all atelectatic, edematous, or fluid-filled alveoli and an aerated lung unit representing well-aerated alveoli. Physiologic parameters in the models were identified by minimizing the error between the simulated and measured data. The model was used to simulate data collected from normal sheep in the prone position, and from sheep experimentally injured with surfactant depletion in both the prone and supine position. Advantages and limitations of the models and identification routines were discussed. In the final chapter, calculations of the shunt fraction, imaged lung fraction, and alveolar gas-volume of tracer distribution were made directly from the PET images and kinetics curves. Assumptions of the calculations were described, and the developed PET and arterial models were used to quantify the associated errors.