Background: Gliomas account for more than 70% of all brain tumors, with median survival times as low as 1 year. Studies show a correlation between maximization of tumor resection and survival/quality of life in this patient population. As such, our group is developing an imaging platform for fluorescence-guided resection (FGR) with the ultimate goal of maximizing tumor removal. Methods: Patients are administered an oral dose of δ-aminolevulinic acid (ALA) prior to surgery, inducing selective accumulation in tumor tissue of the endogenous fluorophore, protoporphyrin IX (PpIX), as a result of metabolic and proliferative changes that differ significantly between normal and tumor tissue. Conventional intraoperative in vivo FGR technologies are not sufficiently sensitive to detect low levels of PpIX fluorescence in low- and high-grade gliomas, thus leaving tumor tissue undetected. Further, in low-grade gliomas, ALA-PpIX FGR has shown no significant value as an imaging modality for surgical guidance, but in this tumor type maximization of tumor removal could have the most significant impact on survival/quality of life. Results: We show the use of a light-transport modeling spectroscopic approach for sensitive intraoperative in vivo quantification down to the ng/ml concentrations of PpIX for real-time (i.e., <0.5 s) FGR of gliomas. Receiver-operating characteristic (ROC) analysis for low- and high-grade glioma cases (n=5) in our clinical study was performed to compare the conventional approach using a fluorescence imaging surgical microscope and our fiber-optics quantitative approach. Our results show significantly improved diagnostic capabilities for tumor tissue detection of our quantitative approach (Fig. 1). Conclusions: We show sensitive and quantitative fluorescence detection of PpIX biomarker for real-time in vivo tumor margin delineation in gliomas, as part of an intraoperative imaging platform for FGR of brain tumors with the goal of providing improved surgical guidance technologies to the neurosurgeon.