Evaluation of the accuracy and precision of lung aerosol deposition measurements from single-photon emission computed tomography using simulation.
ABSTRACT Single-photon emission computed tomography (SPECT) imaging is being increasingly used to assess inhaled aerosol deposition. This study uses simulation to evaluate the errors involved in such measurements and to compare them with those from conventional planar imaging. SPECT images of known theoretical distributions of radioaerosol in the lung have been simulated using lung models derived from magnetic resonance studies in human subjects. Total lung activity was evaluated from the simulated images. A spherical transform of the lung distributions was performed, and the absolute penetration index (PI) and a relative value expressed as a fraction of that in a simulated ventilation image were calculated. All parameters were compared with the true value used in the simulation, and the errors were assessed. An iterative method was used to correct for the partial volume effect, and its effectiveness in improving errors was evaluated. The errors were compared with those of planar imaging. The precision of measurements was significantly better for SPECT than planar imaging (2.8 vs 6.3% for total lung activity, 6 vs 20% for PI, and 3 vs 6% for relative PI). The method of correcting for the influence of the partial volume effect significantly improved the accuracy of PI evaluation without affecting precision. SPECT is capable of accurate and precise measurements of aerosol distribution in the lung, which are improved compared with those measured by conventional planar imaging. A technique for correcting the SPECT data for the influence of the partial volume effect has been described. Simulation is demonstrated as a valuable method of technique evaluation and comparison.
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ABSTRACT: Abstract Background: Determination of the lung outline and regional lung air volume is of value in analysis of three-dimensional (3D) distribution of aerosol deposition from radionuclide imaging. This study describes a technique for using computed tomography (CT) scans for this purpose. Methods: Low-resolution CT scans of the thorax were obtained during tidal breathing in 11 healthy control male subjects on two occasions. The 3D outline of the lung was determined by image processing using minimal user interaction. A 3D map of air volume was derived and total lung air volume calculated. The regional distribution of air volume from center to periphery of the lung was analyzed using a radial transform and the outer-to-inner ratio of air volume determined. Results: The average total air volume in the lung was 1,900±126 mL (1 SEM), which is in general agreement with the expected value for adult male subjects in the supine position. The fractional air volume concentration increased from the center toward the periphery of the lung. Outer-to-inner (O/I) ratios were higher for the left lung [11.5±1.8 (1 SD)] than for the right [10.1±0.8 (1 SD)] (p<0.001). When normalized for the region sizes, these ratios were 1.37±0.16 and 1.20±0.04, respectively. The coefficient of variation of repeated measurement of the normalized O/I ratio was 5.9%. Conclusions: A technique for outlining the lungs from CT images and obtaining an image of the distribution of air volume is described. The normal range of various parameters describing the regional distribution of air volume is presented, together with a measure of intrasubject repeatability. This technique and data will be of value in analyzing 3D radionuclide images of aerosol deposition.Journal of Aerosol Medicine and Pulmonary Drug Delivery 03/2013; · 2.89 Impact Factor
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ABSTRACT: Interest in bioequivalence (BE) of inhaled drugs derives largely from the desire to offer generic substitutes to successful drug products. The complexity of aerosol dosage forms renders them difficult to mimic and raises questions regarding definitions of similarities and those properties that must be controlled to guarantee both the quality and the efficacy of the product. Despite a high level of enthusiasm to identify and control desirable properties there is no clear guidance, regulatory or scientific, for the variety of aerosol dosage forms, on practical measures of BE from which products can be developed. As more data on the pharmaceutical and clinical relevance of various techniques, as described in this review, become available, it is likely that a path to the demonstration of BE will become evident. In the meantime, debate on this topic will continue.Therapeutic delivery 03/2013; 4(3):343-67.
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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 24 h 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.Journal of Aerosol Science 01/2012; 52:1–17. · 2.69 Impact Factor