Researchers at the Perelman School of Medicine at the University of Pennsylvania (Philadelphia, PA) have developed a fluorescence imaging tool that makes tumors glow brightly during surgery.
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In a new study, the fluorescence method—originally developed by surgeons at the Penn Center for Precision Surgery to treat lung cancer—illuminated brain tumors in real time during surgery, helping physicians distinguish between healthy and cancerous tissue.
The technique uses near-infrared (NIR) imaging and the contrasting agent indocyanine green (ICG), which fluoresces a bright green under NIR light. ICG was developed during World War II as a dye in photography and, in 1958, it was approved by the FDA for use in medicine, primarily in liver diagnostics and later in cardiology. However, for this study, the researchers used a modified version of ICG at a higher concentration delivered intravenously about 24 hours before surgery to ensure margins were included. This is the first time, to the authors knowledge, that this delayed imaging of ICG has been used to visualize brain tumors.
Patients enrolled in the clinical study were between the ages of 20 and 81 with a diagnosis of a solitary brain tumor and a presumed glioma based on imaging or prior surgery or biopsy. Twelve of the 15 tumors demonstrated strong intraoperative fluorescence. The lack of glow in the three remaining tumors could potentially be due to their disease grade and timing of the injection, the authors suggest.
Eight of the 15 patients demonstrated a visible glow through the dura (a thick membrane on the meninges of the brain), demonstrating the technology's ability to see deeply within the brain before the tumor is exposed. Once opened, all tumors were picked up by NIR imaging.
The researchers also studied the surgical margins using neuropathology and magnetic resonance imaging (MRI) to assess the accuracy and precision of NIR fluorescence in identifying tumor tissue. Of the 71 specimens collected from MRI-enhanced tumors and their surgical margins, 61 (85.9%) fluoresced and 51 of these (71.8%) were classified as glioma tissue.
Of the 12 MRI-enhancing gliomas, four patients had biopsy specimens that were both non-fluorescent and negative for tumor, which matched the gross total resection seen on their MRI. In contrast, eight patients had residual fluorescent signal in the resection cavity. Only three of these patients showed gross total resection on MRI. This suggests a benefit of true-negative NIR signal after resection, the authors say.
"This technique, if approved by the FDA, may offer great promise to physicians and patients," says study co-author Sunil Singhal, MD, an associate professor of surgery and co-director the Center for Precision Surgery at the Abramson Cancer Center. "It's a strategy that could allow greater precision across many different cancer types, help with early detection, and hopefully better treatment success."
Full details of the work appear in the journal Neurosurgery; for more information, please visit http://dx.doi.org/10.1227/neu.0000000000001450.
