Intraoperative Near-Infrared Optical Contrast Can Localize Brain Metastases.

Introduction: Approximately 100,000 brain metastases are diagnosed annually in the United States. Our laboratory has pioneered a novel technique, second window indocyanine green (SWIG), which allows for real-time intraoperative visualization of brain metastasis through normal brain parenchyma and intact dura.

Methods: Thirteen patients with intraparenchymal brain metastases were administered indocyanine green (ICG) at 5 mg/kg the day before surgery. A near-infrared (NIR)- capable camera was used intraoperatively to identify the tumor and to inspect surgical margins. Neuropathology was used to assess the accuracy and precision of the fluorescent dye for identifying tumor.

Results: ICG was infused at 24.7 ± 3.45 hours before visualization. All 13 metastases fluoresced with an average signal-to-background ratio (SBR) of 6.62. The SBR with the dura intact was 67.2% of the mean SBR once the dura was opened. The NIR signal could be visualized through normal brain parenchyma up to 7 mm. For the 39 total specimens, the mean SBR for tumor specimens (n = 28) was 6.9, whereas the SBR for nontumor specimens (n = 11) was 3.7. The sensitivity, specificity, positive predictive value, and negative predictive value of NIR imaging for tumor was 96.4%, 27.3%, 77.1%, and 75.0%.

Discussion: SWIG relies on the passive accumulation of dye in abnormal tumor tissue via the enhanced permeability and retention effect. It provides strong NIR optical contrast, which can be used to localize tumors before dural opening. The use of SWIG for margin assessment remains limited by its lack of specificity (high false-positive rate); however, ongoing improvements in imaging parameters show great potential to reduce false-positive results.