Intraoperative glioma characterization using time-resolved fluorescence spectroscopy

2072 Background: Extent of surgical resection significantly improves progression-free and overall survival in glioma patients. Due to the infiltrative nature of gliomas, tumor margin detection is often difficult, and current intraoperative visualization methods are limited. Time-resolved fluorescence spectroscopy (TRFS) has the potential of differentiating glioma from normal brain tissue, thereby maximizing extent and safety of resection. Methods: Twenty-seven preoperative patients diagnosed with glioma met inclusion criteria for an IRB-approved study aimed to assess the accuracy of TRFS relative to tissue histopathology for differentiating glioma from normal cortex (NC), normal white matter (NWM), and white matter with edema (WME). A multi-channel TRFS system was developed for in vivo brain tissue and tumor characterization during glioma surgery. A custom-designed fiber optic probe was used to deliver ultrafast laser pulses to tissue regions of interest and collect fluorescence signals, with simultaneous registration to intraoperative neuronavigation. The fluorescence light was collected using a photomultiplier tube and digitized across six wavelength bands. Biopsies were taken at each measurement site for evaluation by a blinded neuropathologist to determine the accuracy of TRFS, which was calculated using parameters derived from the recorded fluorescence pulse and used to characterize tissue signatures. Results: During surgical resection of 27 patients, 162TRFS measurements were collected in vivo followed by biopsy of the same tissue. Samples from brain tumors (39 low grade gliomas (LGG, WHO grade I to III), 35 high grade gliomas (HGG, WHO grade IV)) were compared with 47 samples of normal brain tissue (NC and NWM). The time-resolved system was able to differentiate LGG from normal tissue with 97% sensitivity and 93% specificity (93% PPV and 98% NPV). When all tumor grades were tested, the sensitivity dropped to 91% (96% PPV and 86% NPV), which we believe reflects the heterogeneity of HGG. HGG alone showed a sensitivity of 83% and specificity of 93% (91% PPV and 88% NPV). Normal cortex had the fastest decays across all wavelength bands among different tissue types, WME had longer decays compared to other tissue types at all wavelengths, and HGG had a variable but predictably different fluorescence decay pattern. Conclusions: TRFS is an intraoperative tool that can distinguish glioma from normal brain tissue and has the potential to maximize safe surgical resection.