CLINICAL ARTICLE J Neurosurg 122:40–48, 2015 J Neurosurg Volume 122 • January 2015 F OR maximizing overall and recurrence-free survival in patients with low- and high-grade gliomas, the ex- tent of resection is critical. 9,10 However, the margins between neoplastic tissue and normal parenchyma are of- ten difficult to distinguish intraoperatively by macroscop- ic or microscopic visualization. The optical properties of neoplastic tissue and normal parenchyma can be similar. The transition from neoplastic to normal tissue can also be poorly demarcated, with indistinct transitions between these tissue types at the microscopic level. A major ad- vance in the surgical treatment of these intraaxial patholo- gies was the use of preoperative MRI as an intraoperative aid in the form of stereotactic guidance. However, “brain shift” caused by loss of CSF, cyst decompression, tumor Intraoperative stereotactic injection of Indigo Carmine dye to mark ill-defined tumor margins: a prospective Phase I–II study Konstantinos Margetis, MD, 1 Prajwal Rajappa, MD, 1 Apostolos John Tsiouris, MD, 2 Jeffrey P. Greenfield, MD, PhD, 1 and Theodore H. Schwartz, MD, 1,3–5 Departments of 1 Neurological Surgery, 2 Radiology, 3 Otorhinolaryngology, and 4 Neurology, Brain and Spine Center; and 5 Department of Neuroscience, Brain and Mind Institute, Weill Cornell Medical College, NewYork-Presbyterian Hospital, New York, New York OBJECT 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 inject- ed 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. Clinical trial registration no.: NCT01767415 (clinicaltrials.gov) http://thejns.org/doi/abs/10.3171/2014.9.JNS14113 Key WoRDS extent of resection; glioma; Indigo Carmine; frameless stereotaxy; neuronavigation; oncology AbbReviATionS 5-ALA = 5-aminolevulinic acid; ETL = echo-train length; IND = Investigational New Drug; NEX = number of excitations. SubMiTTeD January 16, 2014. ACCEPTED September 25, 2014. inCluDe WHen CiTinG Published online October 31, 2014; DOI: 10.3171/2014.9.JNS14113. DiSCloSuRe The study was supported by the Department of Neurological Surgery of Weill Cornell Medical College. The authors have no personal, financial, or institu- tional interest in any of the drugs, materials, or devices described in this article. 40 ©AANS, 2015