title: Analysis of three-dimensional aerosol deposition in pharmacologically relevant terms: beyond black or white ROIs.
abstract: BACKGROUND
  This article presents a novel methodological approach to evaluate images of aerosol deposition taken with PET-CT cameras. Traditionally, Black-or-White (BW) Regions of Interest (ROIs) are created to cover Anatomical Regions (ARs) segmented from the high-resolution CT. Such ROIs do not usually consider blurring effects due to limited spatial resolution or breathing motion, and do not consider uncertainty in the AR position within the PET image. The new methodology presented here (Grayscale) addresses these issues, allows estimates of aerosol deposition within ARs, and expresses the deposition in terms of Tissue Dosing (in the lung periphery) and Inner Surface Concentration (in the larger airways).
  
  
  METHODS
  Imaging data included a PET deposition image acquired during breathing and two CT scans acquired during breath holds at different lung volumes. The lungs were segmented into anatomically consistent ARs to allow unbiased comparisons across subjects and across lobes. The Grayscale method involves defining Voxel Influence Matrices (VIMs) to consider how average activity within each AR influences the measured activity within each voxel. The BW and Grayscale methods were used to analyze aerosol deposition in 14 bronchoconstricted asthmatics.
  
  
  RESULTS
  Grayscale resulted in a closer description of the PET image than BW (p<0.0001) and exposed a seven-fold underestimation in measures of specific deposition. The Average Tissue Dosing was 2.11×10(-6) Total Lung Dose/mg. The average Inner Surface Concentration was 45×10(-6) Total Lung Dose/mm(2), with the left lower lobe having a lower ISC than lobes of the right lung (p<0.05). There was a strong lobar heterogeneity in these measures (COV=0.3).
  
  
  CONCLUSIONS
  The Grayscale approach is an improvement over the BW approach and provides a closer description of the PET image. It can be used to characterize heterogeneous concentrations throughout the lung and may be important in translational research and in the evaluation of aerosol delivery systems.
authors: 1 Department of Mechanical Engineering, Massachusetts Institute of Technology , Cambridge, MA, 02142.
authors: Elliot Eliyahu
authors: EE
authors: Greenblatt
authors: Tilo
authors: T
authors: Winkler
authors: Robert Scott
authors: RS
authors: Harris
authors: Vanessa Jane
authors: VJ
authors: Kelly
authors: Mamary
authors: M
authors: Kone
authors: Jose
authors: J
authors: Venegas
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D001249:Asthma / Q000000981:diagnostic imaging* / Q000503:physiopathology; D016084:Bronchoconstriction; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008168:Lung / Q000000981:diagnostic imaging* / Q000503:physiopathology; D008297:Male; D061330:Multidetector Computed Tomography / Q000295:instrumentation; D064847:Multimodal Imaging / Q000295:instrumentation; D009330:Nebulizers and Vaporizers; D049268:Positron-Emission Tomography / Q000295:instrumentation; D012965:Sodium Chloride / Q000008:administration & dosage* / Q000737:chemistry; D055815:Young Adult
chemical_list: D000336:Aerosols; D012965:Sodium Chloride
keywords: PET-CT; ROIs; heterogeneity; motion correction; mucocilliary transport; partial volume effect; spillover effect; surface concentration; tissue dosing