title: Controlled, Parametric, Individualized, 2-D and 3-D Imaging Measurements of Aerosol Deposition in the Respiratory Tract of Asthmatic Human Subjects for Model Validation.
abstract: BACKGROUND
  Computer modeling is used to predict inhaled aerosol deposition in the lung based on definition of the aerosol characteristics and the breathing pattern and airway anatomy of the subject. Validation of the models is limited by the lack of detailed experimental data. Three-dimensional imaging provides an opportunity to address this unmet need.
  
  
  METHODS
  Radioactive aerosol was administered to six male asthmatic subjects on two occasions under carefully monitored input conditions. Input parameters varied in particle size, depth of breathing, and carrier gas. The aerosol distribution was measured by combined single photon emission computed tomography and x-ray computer tomography (SPECT/CT) and airway anatomy by high resolution CT. The deposition distribution was measured by both a 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 subdivisions within each lung. The percentage deposition in the conducting airways was also assessed by 24 h clearance.
  
  
  RESULTS
  A set of imaging data of aerosol deposition has thus been produced in which the input parameters of inhalation are well described. The results in asthmatics were compared to previous measurements in healthy controls using an identical inhalation protocol. The percentages of deposition in extra-thoracic and thoracic compartments of the airways were not significantly affected by disease, but the regional pulmonary deposition pattern was, with asthma leading to increased deposition in the conducting airways.
  
  
  CONCLUSIONS
  The dataset acquired in this study will be useful in validating computer models of aerosol deposition in asthmatic subjects. Asthma did not affect the fraction of inhaled aerosol depositing in the lungs, but gave rise to a more central deposition pattern. The use of 3D SPECT imaging in combination with 24 h clearance measurements enables differentiation of deposition between bronchial and bronchiolar airways.
authors: 1 National Institute of Health Research Biomedical Research Unit in Respiratory Disease , Southampton, United Kingdom .|2 Department of Medical Physics and Bioengineering, University Hospital Southampton NHS Foundation Trust , Southampton, United Kingdom .|4 Medical R&D, Air Liquide Santé International, Paris-Saclay Research Center , Les Loges-en-Josas, France .
authors: John
authors: J
authors: Fleming
authors: 1 National Institute of Health Research Biomedical Research Unit in Respiratory Disease , Southampton, United Kingdom .|3 Faculty of Health Sciences, University of Southampton , Southampton, United Kingdom .
authors: Joy
authors: J
authors: Conway
authors: 4 Medical R&D, Air Liquide Santé International, Paris-Saclay Research Center , Les Loges-en-Josas, France .
authors: Caroline
authors: C
authors: Majoral
authors: 4 Medical R&D, Air Liquide Santé International, Paris-Saclay Research Center , Les Loges-en-Josas, France .|5 Department of Mechanical Engineering, Lafayette College , Easton, Pennsylvania.
authors: Ira
authors: I
authors: Katz
authors: 4 Medical R&D, Air Liquide Santé International, Paris-Saclay Research Center , Les Loges-en-Josas, France .
authors: Georges
authors: G
authors: Caillibotte
authors: 4 Medical R&D, Air Liquide Santé International, Paris-Saclay Research Center , Les Loges-en-Josas, France .
authors: Marine
authors: M
authors: Pichelin
authors: 4 Medical R&D, Air Liquide Santé International, Paris-Saclay Research Center , Les Loges-en-Josas, France .
authors: Spyridon
authors: S
authors: Montesantos
authors: 1 National Institute of Health Research Biomedical Research Unit in Respiratory Disease , Southampton, United Kingdom .
authors: Michael
authors: M
authors: Bennett
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000336:Aerosols; D001249:Asthma / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D021621:Imaging, Three-Dimensional; D008168:Lung / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D064847:Multimodal Imaging / Q000379:methods*; D010316:Particle Size; D011237:Predictive Value of Tests; D019275:Radiopharmaceuticals / Q000008:administration & dosage* / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D015656:Respiratory Mechanics; D065589:Respiratory Tract Absorption; D013668:Technetium Tc 99m Aggregated Albumin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed; D055815:Young Adult
chemical_list: D000336:Aerosols; D019275:Radiopharmaceuticals; D013668:Technetium Tc 99m Aggregated Albumin; C083602:technetium Tc 99m nanocolloid
keywords: aerosol deposition; asthma; experimental measurements; helium–oxygen; imaging