title: Minimally invasive electro-magnetic navigational bronchoscopy-integrated near-infrared-guided sentinel lymph node mapping in the porcine lung.
abstract: BACKGROUND
  The use of near-infrared (NIR) fluorescence imaging with indocyanine green (ICG) for sentinel lymph node (SN) mapping has been investigated in lung cancer; however, this has not been fully adapted for minimally invasive surgery (MIS). The aim of our study was to develop a minimally invasive SN mapping integrating pre-operative electro-magnetic navigational bronchoscopy (ENB)-guided transbronchial ICG injection and intraoperative NIR thoracoscopic imaging.
  
  
  METHODS
  A NIR thoracoscope was used to visualize ICG fluorescence. ICG solutions in a 96-well plate and ex vivo porcine lungs were examined to optimize ICG concentrations and injection volumes. Transbronchial ICG injection (n=4) was assessed in comparison to a traditional transpleural approach (n=3), where after thoracotomy an ICG solution (100 μL at 100 μg/mL) was injected into the porcine right upper lobe for SN identification. For further translation into clinical use, transbronchial ICG injection prior to thoracotomy followed by NIR thoracoscopic imaging was validated (n=3). ENB was used for accurate targeting in two pigs with a pseudo-tumor.
  
  
  RESULTS
  The ICG fluorescence at 10 μg/mL was the brightest among various concentrations, unchanged by the distance between the thoracoscope and ICG solutions. Injected ICG of no more than 500μ L showed a localized fluorescence area. All 7 pigs showed a bright paratracheal lymph node within 15 minutes post-injection, with persistent fluorescence for 60 minutes. The antecedent transbronchial ICG injection succeeded in SN identification in all 3 cases at the first thoracoscopic inspection within 20 minutes post-injection. The ENB system allowed accurate ICG injection surrounding the pseudo-tumors.
  
  
  CONCLUSIONS
  ENB-guided ICG injection followed by NIR thoracoscopy was technically feasible for SN mapping in the porcine lung. This promising platform may be translated into human clinical trials and is suited for MIS.
authors.affiliation: Division of Thoracic Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada; Department of General Thoracic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Wada
authors.affiliation: Division of Thoracic Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Hirohashi
authors.affiliation: Division of Thoracic Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
authors.forename: Takashi
authors.initials: T
authors.lastname: Anayama
authors.affiliation: Division of Thoracic Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada; Department of General Thoracic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nakajima
authors.affiliation: Division of Thoracic Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kato
authors.affiliation: Guided Therapeutics, TECHNA Institute, University Health Network, Toronto, Ontario, Canada.
authors.forename: Harley H L
authors.initials: HH
authors.lastname: Chan
authors.affiliation: Guided Therapeutics, TECHNA Institute, University Health Network, Toronto, Ontario, Canada.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Qiu
authors.affiliation: Guided Therapeutics, TECHNA Institute, University Health Network, Toronto, Ontario, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Daly
authors.affiliation: Guided Therapeutics, TECHNA Institute, University Health Network, Toronto, Ontario, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Weersink
authors.affiliation: Guided Therapeutics, TECHNA Institute, University Health Network, Toronto, Ontario, Canada.
authors.forename: David A
authors.initials: DA
authors.lastname: Jaffray
authors.affiliation: Guided Therapeutics, TECHNA Institute, University Health Network, Toronto, Ontario, Canada; Department of Otolaryngology, Head and Neck Surgery/Surgical Oncology, Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Irish
authors.affiliation: Division of Thoracic Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Waddell
authors.affiliation: Division of Thoracic Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
authors.forename: Shaf
authors.initials: S
authors.lastname: Keshavjee
authors.affiliation: Department of General Thoracic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Yoshino
authors.affiliation: Division of Thoracic Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada; Guided Therapeutics, TECHNA Institute, University Health Network, Toronto, Ontario, Canada.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yasufuku
mesh_terms: D000818:Animals; D001980:Bronchi / Q000473:pathology; D001999:Bronchoscopy / Q000379:methods*; D004574:Electromagnetic Fields; D005453:Fluorescence; D007208:Indocyanine Green; D007267:Injections; D008168:Lung / Q000473:pathology*; D008198:Lymph Nodes / Q000473:pathology; D010994:Pleura / Q000473:pathology; D021701:Sentinel Lymph Node Biopsy / Q000379:methods*; D019265:Spectroscopy, Near-Infrared / Q000379:methods*; D013997:Time Factors
chemical_list: D007208:Indocyanine Green