title: Identification of breast cancer margins using intraoperative near-infrared imaging.
abstract: OBJECTIVE
  Current methods of intraoperative breast cancer margin assessment are labor intensive, not fully reliable, and time consuming; therefore novel strategies are necessary. We hypothesized that near infrared (NIR) intraoperative molecular imaging using systemic indocyanine green (ICG) would be helpful in discerning tumor margins.
  
  
  METHODS
  A mammary cancer cell line, 4T1, was used to establish tumors in mouse flanks (n = 60). Tumors were excised 24 hr after intravenous ICG. Assessment of residual tumor in the wound bed was performed using a combination of NIR imaging and traditional method (by visual inspection and palpation) versus traditional method alone. Next we performed a clinical trial to evaluate the role of NIR imaging after systemic ICG for the margin assessment of 12 patients undergoing breast-conserving surgery.
  
  
  RESULTS
  Traditional margin assessment identified 30% of positive margins while NIR imaging identified 90% of positive margins. In our clinical trial, all tumors were detected by NIR imaging and there was fluorescent evidence of residual tumor in the tumor bed in 6 of the 12 patients. None of these patients had positive margins on pathology.
  
  
  CONCLUSIONS
  Systemic ICG reliably accumulates in breast cancers in murine models as well as human breast cancer. While NIR imaging is helpful for detection of retained tumor margins in our animal model, intraoperative imaging for precise margin detection will need further refinement before clinical value can be obtained. J. Surg. Oncol. 2016;113:508-514. © 2016 Wiley Periodicals, Inc.
authors: Department of Thoracic Surgery, University of Pennsylvania, Perelman School of Medicine, 3400 Spruce Street, Philadelphia, Pennsylvania.
authors: Jane
authors: J
authors: Keating
authors: Department of Thoracic Surgery, University of Pennsylvania, Perelman School of Medicine, 3400 Spruce Street, Philadelphia, Pennsylvania.
authors: Julia
authors: J
authors: Tchou
authors: Department of Thoracic Surgery, University of Pennsylvania, Perelman School of Medicine, 3400 Spruce Street, Philadelphia, Pennsylvania.
authors: Olugbenga
authors: O
authors: Okusanya
authors: Department of Thoracic Surgery, University of Pennsylvania, Perelman School of Medicine, 3400 Spruce Street, Philadelphia, Pennsylvania.
authors: Carla
authors: C
authors: Fisher
authors: Department of Pathology, University of Pennsylvania, Perelman School of Medicine, 3400 Spruce Street, Philadelphia, Pennsylvania.
authors: Rebecca
authors: R
authors: Batiste
authors: Department of Thoracic Surgery, University of Pennsylvania, Perelman School of Medicine, 3400 Spruce Street, Philadelphia, Pennsylvania.
authors: Jack
authors: J
authors: Jiang
authors: Department of Thoracic Surgery, University of Pennsylvania, Perelman School of Medicine, 3400 Spruce Street, Philadelphia, Pennsylvania.
authors: Gregory
authors: G
authors: Kennedy
authors: Departments of Biomedical Engineering and Chemistry, Emory University, 1364 Clifton Road, Atlanta, Georgia.
authors: Shuming
authors: S
authors: Nie
authors: Department of Thoracic Surgery, University of Pennsylvania, Perelman School of Medicine, 3400 Spruce Street, Philadelphia, Pennsylvania.
authors: Sunil
authors: S
authors: Singhal
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000601:surgery*; D004396:Coloring Agents; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007208:Indocyanine Green; D007430:Intraoperative Care; D000072662:Margins of Excision; D015412:Mastectomy, Segmental; D051379:Mice; D008875:Middle Aged; D057054:Molecular Imaging; D018365:Neoplasm, Residual; D010865:Pilot Projects; D019265:Spectroscopy, Near-Infrared
chemical_list: D004396:Coloring Agents; D007208:Indocyanine Green
keywords: indocyanine green; molecular imaging; solid tumor