title: Intraoperative stereotactic injection of Indigo Carmine dye to mark ill-defined tumor margins: a prospective phase I-II study.
abstract: OBJECTIVE
  A critical goal in neurosurgical oncology is maximizing the extent of tumor resection while minimizing the risk to normal white matter tracts. Frameless stereotaxy and white matter mapping are indispensable tools in this effort, but deep tumor margins may not be accurately defined because of the "brain shift" at the end of the operation. The authors investigated the safety and efficacy of a technique for marking the deep margins of intraaxial tumors with stereotactic injection of Indigo Carmine dye.
  
  
  METHODS
  Investigational New Drug study approval for a prospective study in adult patients with gliomas was obtained from the FDA (Investigational New Drug no. 112680). At surgery, 1-3 stereotactic injections of 0.01 ml of Indigo Carmine dye were performed through the initial bur holes into the deep tumor margins before elevation of the bone flap. White light microscopic resection was conducted in standard fashion by using frameless stereotactic navigation until the injected margins were identified. The resection of the injected tumor margins and the extent of resection of the whole tumor volume were determined by using postoperative volumetric MRI.
  
  
  RESULTS
  In total 17 injections were performed in 10 enrolled patients (6 male, 4 female), whose mean age was 49 years. For all patients, the injection points were identified intraoperatively and tumor was resected at these points. The staining pattern was reproducible; it was a sphere of stained tissue approximately 5 mm in diameter. A halo of stained tissue and a backflow of dye through the needle tract were also noted, but these were clearly distinct from the staining pattern of the injection point, which was vividly colored and demarcated. Postoperative MR images verified the resection of all injection points. The mean extent of resection of the tumor as a whole was 97.1%. For 1 patient, a brain abscess developed on postoperative Day 16 and needed additional surgical treatment.
  
  
  CONCLUSIONS
  Stereotactic injection of Indigo Carmine dye can be used to demarcate multiple deep tumor margins, which can be readily identified intraoperatively by using standard white light microscopy. This technique may enhance the accuracy of frameless stereotactic navigation and increase the extent of resection of intraaxial tumors.
authors.affiliation: Departments of 1 Neurological Surgery.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Margetis
authors.forename: Prajwal
authors.initials: P
authors.lastname: Rajappa
authors.forename: Apostolos John
authors.initials: AJ
authors.lastname: Tsiouris
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Greenfield
authors.forename: Theodore H
authors.initials: TH
authors.lastname: Schwartz
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000601:surgery*; D002102:Cadaver; D004396:Coloring Agents / Q000008:administration & dosage; D005260:Female; D005910:Glioma / Q000601:surgery*; D006801:Humans; D007203:Indigo Carmine / Q000008:administration & dosage; D007432:Intraoperative Period; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D038361:Neuronavigation / Q000379:methods*; D019635:Neurosurgical Procedures / Q000379:methods*; D011446:Prospective Studies
chemical_list: D004396:Coloring Agents; D007203:Indigo Carmine
keywords: 5-ALA = 5-aminolevulinic acid; ETL = echo-train length; IND = Investigational New Drug; Indigo Carmine; NEX = number of excitations; extent of resection; frameless stereotaxy; glioma; neuronavigation; oncology