Postdeposition dispersion of aerosol medications using surfactant carriers.

Inhaled aerosol drugs provide a means of directly treating the lungs; however, aerosol deposition and drug distribution can be nonuniform, especially in obstructive lung disease. We hypothesize that surfactant-based aerosol carriers will disperse medications over airway surfaces after deposition through surface tension driven flows, increasing dose uniformity and improving drug distribution into underventilated regions. We considered saline and surfactant aerosol delivery via cannula onto several model airway surfaces including porcine gastric mucus (PGM) and both cystic fibrosis (CF) and non-CF human bronchial epithelial cells (HBEs). Fluorescent dye and microspheres (d = 100 nm, 1 mum) were used to qualitatively and quantitatively assess postdeposition dispersion. Aerosol volume median diameters were in the 1-4 mum range. The tested surfactants included sodium dodecyl sulfate (SDS), cetyl trimethyl ammonium bromide (CTAB), tyloxapol, and calfactant. All surfactants tested on PGM (tyloxapol, calfactant, SDS, and CTAB) significantly increased dispersion area versus saline with all markers (2-20-fold increases; all p < 0.04). Both surfactants tested on CF HBEs (tyloxapol and calfactant) significantly increased dispersion area versus saline with all markers (1.6-4.1-fold increases; all p

Aerosol delivery through nasal cannulas: an in vitro study.

In most circumstances, a nasal route for the delivery of pulmonary aerosol medications is rarely considered; however, in specific instances, this route may be quite useful. Consider, for example, the delivery of aerosol treatments during humidified high-flow nasal cannula use in pediatric critical care, or continuous aerosol delivery via cannula for medications with short durations of action. The goal of this study was to evaluate the potential for delivering aerosols via nasal cannula through in vitro studies of aerosol output and size. The system utilized for testing included an Aerogen Solo nebulizer downstream of a heater/humidifier system, followed by a nasal cannula and an aerosol collection apparatus. Adult, pediatric, and infant cannulas were tested with and without an inhalation-only breathing simulator. The cannulas were driven by 3 lpm (50 psig) oxygen flows. Dose quantification was performed using radioisotope techniques. Total cannula output and system losses were measured. Aerosol size measurements were made from the nebulizer, from the heating tube, and from the prongs of the adult and pediatric cannulas, using laser-diffraction techniques. Total cannula output ranged from 8.4-25.1% and 18.6-26.9% of loaded dose, without and with the addition of inhalation flows. Volume median diameters were 2.2 +/- 0.2 microm from the adult cannula and 1.9 +/- 0.3 microm from the pediatric cannula. Ninety percent of the aerosol volume was in sizes smaller than 4.2 +/- 0.4 microm (adult) and 3.8 +/- 0.5 microm (pediatric). System losses were highest in the nebulizer-humidifier connectors, heated tube, and humidifier. Losses in the nebulizer were very low (2.2-3.5%). This study demonstrates that aerosols can be efficiently delivered through a humidified high-flow nasal cannula system. Further study is required to determine if this route is viable for pulmonary delivery.

Enhanced parameter estimation from noisy PET data: Part II--evaluation.

RATIONALE AND OBJECTIVES: Positron emission tomography (PET) is a minimally invasive imaging modality that provides three-dimensional distribution data for a radioactive tracer concentration within the body. Local functional parameters are estimated from these images by fitting tracer kinetic data with mathematical models. However, in some applications, the reliability of parameter estimates may be hindered by the presence of noise. In the accompanying report in this issue of Academic Radiology, a novel method using principal component analysis (PCA) was presented and used for deriving parametric images of lung function from imaged tracer kinetics of intravenously injected nitrogen 13 (13NN) in saline solution. The PCA method averages 13NN concentrations from groups of voxels (volume elements) selected for their similarity in kinetics, rather than their spatial proximity. The goal of this study is to conduct a Monte Carlo simulation to evaluate the robustness to noise of parameters derived by means of the PCA method. MATERIALS AND METHODS: This evaluation involved: (1) generating "noise-free" synthetic PET images from experimental PET data, (2) adding noise to these images, (3) applying the PCA method to yield parametric images, and (4) comparing these parametric images with original noise-free images. RESULTS: Local parameters recovered by using the PCA method deviated from noise-free parameters on average by less than 1% for up to 32-fold of expected noise levels. These deviations were much less than those (>10%) recovered by using a direct curve-fitting method. CONCLUSION: The novel PCA approach provides robust parametric lung functional images while preserving the spatial resolution of the original images.