Controlled, parametric, individualized, 2-D and 3-D imaging measurements of aerosol deposition in the respiratory tract of healthy human subjects for model validation

Abstract

Computer modeling is used widely to predict inhaled aerosol deposition in the human lung based on definition of the input conditions describing the aerosol characteristics, the breathing pattern and the airway anatomy of the subject. Validation of the models is limited by the lack of detailed experimental data. Three dimensional imaging data provides an opportunity to address this unmet need. Radioactive aerosol was administered to each of 11 healthy male subjects on two occasions under carefully monitored input conditions. Input parameters varied were particle size, depth of breathing, carrier gas and posture. The aerosol distribution was measured by combined single photon emission computed tomography and X-ray computer tomography (SPECT/CT). Airway anatomy was determined by high resolution CT imaging. The distribution of deposition was determined by a combination of 2D and 3D analysis and described in terms of the percentage of inhaled aerosol deposited in sections of the respiratory tract and in both spatial and anatomical sub-divisions within each lung. The percentage deposition in the conducting airways was also assessed by 24h clearance. A set of imaging data of aerosol deposition has been produced in which the input parameters of inhalation are well described. The parameters were varied in a controlled manner to allow the sensitivity of predictive models to different factors to be tested. An initial analysis of the data is presented which will act as a guide that other centers can use to compare their own methodology. This data is considered to be of great potential value to computer modelers of aerosol deposition in validating their models.