We have had extensive experience with measuring mucociliary clearance as a function of disease status and importantly, in response to therapeutic agents (Figure 18). More recently, these techniques have been extended so that analyses of the heterogeneity of mucus transport as a function of disease status and therapeutic intervention can now be measured (Figure 19).
The inhaled radionucleotide technique can also be utilized for measurements of the total deposition and intraregional deposition of novel therapeutic agents. Thus, we have had extensive experience measuring upper airway, lower airway, and intraregional distributions of inhaled radionuclides as delivered by novel therapeutic devices. This technique is also suitable for performing bridging studies with respect to different devices delivering a common therapeutic agent.
|Figure 18. (Left) radionuclide deposition in normal subject; (Right) acceleration of clearance after inhaled hypertonic saline (HS).||Figure 19. Heterogeneity of mucus clearance in right lung of CF subject.|
In addition to classical CT imaging techniques, we have recently advanced the utilization of MRI for investigation of pulmonary disease and therapeutics directed towards restoration of pulmonary function. Novel techniques include state-of-the-art algorithms to generate detailed structural information about the lung from MRI, utilization of measurements of blood flow to generate insights into airway plugging, and soon, the ability to use hyperpolarized xenon to generate measurements of gas distribution to complete the characterization of the lung by this powerful, non-radiation exposing technique.