title: Intraoperative near-infrared imaging can distinguish cancer from normal tissue but not inflammation.
abstract: BACKGROUND
  Defining tumor from non-tumor tissue is one of the major challenges of cancer surgery. Surgeons depend on visual and tactile clues to select which tissues should be removed from a patient. Recently, we and others have hypothesized near-infrared (NIR) imaging can be used during surgery to differentiate tumors from normal tissue.
  
  
  METHODS
  We enrolled 8 canines and 5 humans undergoing cancer surgery for NIR imaging. The patients were injected with indocyanine green (ICG), an FDA approved non-receptor specific NIR dye that accumulates in hyperpermeable tissues, 16-24 hours prior to surgery. During surgery, NIR imaging was used to discriminate the tumor from non-tumor tissue.
  
  
  RESULTS
  NIR imaging identified all tumors with a mean signal-to-background ratio of 6.7. Optical images were useful during surgery in discriminating normal tissue from cancer. In 3 canine cases and 1 human case, the tissue surrounding the tumor was inflamed due to obstruction of the vascular supply due to mass effect. In these instances, NIR imaging could not distinguish tumor tissue from tissue that was congested, edematous and did not contain cancer.
  
  
  CONCLUSIONS
  This study shows that NIR imaging can identify tumors from normal tissues, provides excellent tissue contrast, and it facilitates the resection of tumors. However, in situations where there is significant peritumoral inflammation, NIR imaging with ICG is not helpful. This suggests that non-targeted NIR dyes that accumulate in hyperpermeable tissues will have significant limitations in the future, and receptor-specific NIR dyes may be necessary to overcome this problem.
authors: Department of Clinical Studies, University of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania, United States of America.
authors: David
authors: D
authors: Holt
authors: Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America.
authors: Olugbenga
authors: O
authors: Okusanya
authors: Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America.
authors: Ryan
authors: R
authors: Judy
authors: Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America.
authors: Ollin
authors: O
authors: Venegas
authors: Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America.
authors: Jack
authors: J
authors: Jiang
authors: Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America.
authors: Elizabeth
authors: E
authors: DeJesus
authors: Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America.
authors: Evgeniy
authors: E
authors: Eruslanov
authors: Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America.
authors: Jon
authors: J
authors: Quatromoni
authors: Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America.
authors: Pratik
authors: P
authors: Bhojnagarwala
authors: Department of Pathology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America.
authors: Charuhas
authors: C
authors: Deshpande
authors: Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America.
authors: Steven
authors: S
authors: Albelda
authors: Departments of Biomedical Engineering and Chemistry, Emory University, Atlanta, Georgia, United States of America.
authors: Shuming
authors: S
authors: Nie
authors: Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America.
authors: Sunil
authors: S
authors: Singhal
mesh_terms: D000368:Aged; D000818:Animals; D045744:Cell Line, Tumor; D003952:Diagnostic Imaging / Q000379:methods*; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D006801:Humans; D007208:Indocyanine Green; D007249:Inflammation / Q000175:diagnosis; D007432:Intraoperative Period; D008175:Lung Neoplasms / Q000175:diagnosis / Q000473:pathology / Q000601:surgery; D051379:Mice; D008875:Middle Aged; D009367:Neoplasm Staging; D009369:Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery; D019265:Spectroscopy, Near-Infrared / Q000379:methods*; D047368:Tumor Burden
chemical_list: D007208:Indocyanine Green