title: Volumetric optical frequency domain imaging of pulmonary pathology with precise correlation to histopathology.
abstract: BACKGROUND
  Lung cancer is the leading cause of cancer-related mortality. Radiology and bronchoscopy techniques do not have the necessary resolution to evaluate lung lesions on the microscopic scale, which is critical for diagnosis. Bronchial biopsy specimens can be limited by sampling error and small size. Optical frequency domain imaging (OFDI) provides volumetric views of tissue microstructure at near-histologic resolution and may be useful for evaluating pulmonary lesions to increase diagnostic accuracy. Bronchoscopic OFDI has been evaluated in vivo, but a lack of correlated histopathology has limited the ability to develop accurate image interpretation criteria.
  
  
  METHODS
  We performed OFDI through two approaches (airway-centered and parenchymal imaging) in 22 ex vivo lung specimens, using tissue dye to precisely correlate imaging and histology.
  
  
  RESULTS
  OFDI of normal airway allowed visualization of epithelium, lamina propria, cartilage, and alveolar attachments. Carcinomas exhibited architectural disarray, loss of normal airway and alveolar structure, and rapid light attenuation. Squamous cell carcinomas showed nested architecture. Atypical glandular formation was appreciated in adenocarcinomas, and uniform trabecular gland formation was seen in salivary gland carcinomas. Mucinous adenocarcinomas showed alveolar wall thickening with intraalveolar mucin. Interstitial fibrosis was visualized as signal-dense tissue, with an interstitial distribution in mild interstitial fibrotic disease and a diffuse subpleural pattern with cystic space formation in usual interstitial pneumonitis.
  
  
  CONCLUSIONS
  To our knowledge, this study is the first demonstration of volumetric OFDI with precise correlation to histopathology in lung pathology. We anticipate that OFDI may play a role in assessing airway and parenchymal pathology, providing fresh insights into the volumetric features of pulmonary disease.
authors.affiliation: Department of Pathology, Boston; Wellman Center for Photomedicine, Boston; Harvard Medical School, Cambridge.
authors.forename: Lida P
authors.initials: LP
authors.lastname: Hariri
authors.affiliation: Pulmonary and Critical Care Unit, Boston; Wellman Center for Photomedicine, Boston.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Applegate
authors.affiliation: Department of Pathology, Boston; Harvard Medical School, Cambridge.
authors.forename: Mari
authors.initials: M
authors.lastname: Mino-Kenudson
authors.affiliation: Department of Pathology, Boston; Harvard Medical School, Cambridge.
authors.forename: Eugene J
authors.initials: EJ
authors.lastname: Mark
authors.affiliation: Pulmonary and Critical Care Unit, Boston; Harvard Medical School, Cambridge.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Medoff
authors.affiliation: Rheumatology, Allergy and Immunology Division, Massachusetts General Hospital, Boston; Harvard Medical School, Cambridge.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Luster
authors.affiliation: Wellman Center for Photomedicine, Boston; Harvard Medical School, Cambridge; Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA.
authors.forename: Brett E
authors.initials: BE
authors.lastname: Bouma
authors.affiliation: Department of Pathology, Boston; Wellman Center for Photomedicine, Boston; Harvard Medical School, Cambridge; Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA.
authors.forename: Guillermo J
authors.initials: GJ
authors.lastname: Tearney
authors.affiliation: Pulmonary and Critical Care Unit, Boston; Wellman Center for Photomedicine, Boston; Harvard Medical School, Cambridge. Electronic address: msuter@partners.org.
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Suter
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D002288:Adenocarcinoma, Mucinous / Q000473:pathology; D001999:Bronchoscopy / Q000379:methods*; D003528:Carcinoma, Adenoid Cystic / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D006222:Hamartoma / Q000473:pathology; D006801:Humans; D008171:Lung Diseases / Q000473:pathology*; D008175:Lung Neoplasms / Q000473:pathology*; D011658:Pulmonary Fibrosis / Q000473:pathology; D041623:Tomography, Optical Coherence / Q000379:methods*