Intraoperative near Infrared Fluorescent Visualization of Meningiomas

Introduction: Extent of resection remains an important predictor of outcome for patients with meningioma. Visible light fluorescent prodrug such as 5-ALA have been used to identify meningioma in the operating room with varying degrees of success. We sought to improve optical contrast with a drug that fluoresces in the near infrared (NIR) spectrum.

Methods: All patients undergoing intracranial surgery for tumor resection were eligible for this IRB-approved study registered in clinicaltrials.gov. Twenty-four hours prior to surgery, 5 mg/kg of an FDA-approved NIR contrast agent was administered intravenously. Intermittently, during surgery, a near infrared camera with excitation light of 805nm was used to photo-document the presence of NIR signal. Margin specimens were obtained, and the presence or absence of tumor based on visible light and NIR light was recorded in binary format (yes/no).

Results: Twenty-two patients were enrolled in this preliminary, proof of concept study. All twenty-two meningiomas demonstrated strong near infrared signal with a signal to background ratio of 4.6 +/− 2.5. Imaging was performed on average 23 +/− 2.3 hours after IV injection of second window ICG. A total of 22 gross tumors and 38 margin samples were studied. Dye remained confined within meningioma in 18 of 22 patients, but in 4 patients an “inversion” pattern was identified which appears to be related to time from injection. Sensitivity of bright light alone for meningioma detection using pathology as gold standard was 85.0%; Sensitivity of NIR was 97.5%. In contrast, specificity of bright light alone was 90.0%; Specificity of NIR was 30.0%.

Conclusion: This study demonstrates that Second Window ICG (SWIG) can be administered at high doses 24 hours prior to surgery. Despite having a half-life measured in minutes, ICG remains contained within meningiomas at sufficient concentration to serve as a tumor marker via the Enhanced Permeability and Retention (EPR) effect. The SWIG technique does not demonstrate vasculature but rather tumor permeability. It appears to be sensitive but nonspecific.