Authors: Steve Cho; Bhavya Khanuga, BS; Love Buch, BS; John Lee (Philadelphia, PA)

Introduction: We previously described a novel technique using the near-infrared (NIR) fluorophore indocyanine-green (ICG) for intraoperative visualization of brain tumors. This technique, termed “Second-Window-ICG” (SWIG), takes advantage of ICG’s accumulation in tissue with enhanced endothelial permeability to detect neoplastic regions. Despite its high sensitivity for neoplastic tissue, prior analysis demonstrated low specificity and positive-predictive-value. Since necrosis and inflammation result in damage to the intracranial vasculature endothelium, we investigated the utility of SWIG in intraoperative visualization of these abnormal changes. Methods: For this IRB-approved study, patients with high-grade gliomas (HGG) or brain metastases were enrolled and 5mg/kg ICG was administered intravenously 24-hours preoperatively. Intraoperatively, NIR imaging of the tumor and post-resection margins was performed using a dedicated NIR-exoscope. The mean signal-to-background-ratios (SBRs) were calculated for all patients and the Mann-Whitney test was used to compare these values in different subgroups of patients. Results: 74 patients (19 untreated metastases, 31 untreated HGG, 10 previously-treated metastases, and 14 previously-treated HGG) were enrolled. Of the 24 patients with prior surgical/radiation treatment, 4 patients displayed necrosis, inflammation, and/or treatment-effect without neoplasm. Despite differences in pathology, all specimens exhibited gadolinium-enhancement and strong ICG-fluorescence. The mean SBR of the gross tumor specimens in-vivo (n=70) was 6.81±2.33 (mean±SD). The mean SBR in-vivo for patients with abnormal tissue but no tumor (n=4) was 8.16±4.49. No significant difference was observed between the two groups using the nonparametric t-test (p=0.94). Furthermore, 14 out of 38 gross glioblastoma specimens contained necrosis with tumor. No significant difference was observed in the mean SBRs between specimens with necrosis+tumor (6.69±2.90) and those with tumor alone (7.34±1.93, p=064). Overall, the sensitivity of SWIG for abnormal tissue detection was 100%. Conclusions: Intraoperative NIR imaging with SWIG, although an accurate indicator of abnormal tissue, currently cannot distinguish neoplasm from necrosis, inflammation and/or treatment-effect.