title: Computer-aided pulmonary image analysis in small animal models.
abstract: OBJECTIVE
  To develop an automated pulmonary image analysis framework for infectious lung diseases in small animal models.
  
  
  METHODS
  The authors describe a novel pathological lung and airway segmentation method for small animals. The proposed framework includes identification of abnormal imaging patterns pertaining to infectious lung diseases. First, the authors' system estimates an expected lung volume by utilizing a regression function between total lung capacity and approximated rib cage volume. A significant difference between the expected lung volume and the initial lung segmentation indicates the presence of severe pathology, and invokes a machine learning based abnormal imaging pattern detection system next. The final stage of the proposed framework is the automatic extraction of airway tree for which new affinity relationships within the fuzzy connectedness image segmentation framework are proposed by combining Hessian and gray-scale morphological reconstruction filters.
  
  
  RESULTS
  133 CT scans were collected from four different studies encompassing a wide spectrum of pulmonary abnormalities pertaining to two commonly used small animal models (ferret and rabbit). Sensitivity and specificity were greater than 90% for pathological lung segmentation (average dice similarity coefficient > 0.9). While qualitative visual assessments of airway tree extraction were performed by the participating expert radiologists, for quantitative evaluation the authors validated the proposed airway extraction method by using publicly available EXACT'09 data set.
  
  
  CONCLUSIONS
  The authors developed a comprehensive computer-aided pulmonary image analysis framework for preclinical research applications. The proposed framework consists of automatic pathological lung segmentation and accurate airway tree extraction. The framework has high sensitivity and specificity; therefore, it can contribute advances in preclinical research in pulmonary diseases.
authors.affiliation: Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, National Institutes of Health (NIH), Bethesda, Maryland 32892.
authors.forename: Ziyue
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Center for Research in Computer Vision (CRCV), University of Central Florida (UCF), Orlando, Florida 32816.
authors.forename: Ulas
authors.initials: U
authors.lastname: Bagci
authors.affiliation: Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, National Institutes of Health (NIH), Bethesda, Maryland 32892.
authors.forename: Awais
authors.initials: A
authors.lastname: Mansoor
authors.affiliation: The Institute of Cancer Research, London SW7 3RP, United Kingdom.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Kramer-Marek
authors.affiliation: Microfluidic Laboratory Automation, University of California-Irvine, Irvine, California 92697-2715.
authors.forename: Brian
authors.initials: B
authors.lastname: Luna
authors.affiliation: Department of Medicine, Imperial College London, London SW7 2AZ, United Kingdom.
authors.forename: Andre
authors.initials: A
authors.lastname: Kubler
authors.affiliation: Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231.
authors.forename: Bappaditya
authors.initials: B
authors.lastname: Dey
authors.affiliation: Department of Biomedical Engineering, University of California-Davis, Davis, California 95817.
authors.forename: Brent
authors.initials: B
authors.lastname: Foster
authors.affiliation: Radiology and Imaging Sciences, National Institutes of Health (NIH), Bethesda, Maryland 32892.
authors.forename: Georgios Z
authors.initials: GZ
authors.lastname: Papadakis
authors.affiliation: Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky 40202.
authors.forename: Jeremy V
authors.initials: JV
authors.lastname: Camp
authors.affiliation: National Institute for Mathematical and Biological Synthesis, University of Tennessee, Knoxville, Tennessee 37996.
authors.forename: Colleen B
authors.initials: CB
authors.lastname: Jonsson
authors.affiliation: Howard Hughes Medical Institute, Chevy Chase, Maryland 20815 and Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231.
authors.forename: William R
authors.initials: WR
authors.lastname: Bishai
authors.affiliation: Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Jain
authors.affiliation: Medical Image Processing Group, Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104.
authors.forename: Jayaram K
authors.initials: JK
authors.lastname: Udupa
authors.affiliation: Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, National Institutes of Health (NIH), Bethesda, Maryland 32892.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Mollura
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005290:Ferric Compounds; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D053118:Influenza A Virus, H1N1 Subtype; D008137:Longitudinal Studies; D008168:Lung / Q000000981:diagnostic imaging*; D008171:Lung Diseases / Q000000981:diagnostic imaging*; D008176:Lung Volume Measurements / Q000379:methods; D000069550:Machine Learning; D009976:Orthomyxoviridae Infections / Q000000981:diagnostic imaging; D011817:Rabbits; D014057:Tomography, X-Ray Computed / Q000379:methods*; D014397:Tuberculosis, Pulmonary / Q000000981:diagnostic imaging
chemical_list: D005290:Ferric Compounds; C035552:ferric gluconate