OBJECT Previous studies in high-grade gliomas (HGGs) have indicated that protoporphyrin IX (PpIX) accumulates in higher concentrations in tumor tissue and when used to guide surgery it has enabled improved resection leading to increased progression-free survival. acid (ALA)-induced PpIX fluorescence in a series of patients with LGG. METHODS Twelve patients with presumed LGGs underwent resection of their tumors after receiving 20 μg/kg of ALA approximately Batimastat (BB-94) 3 hours prior to surgery under an institutional review board-approved protocol. Intraoperative assessments of the resulting PpIX emissions using both qualitative visible fluorescence and quantitative measurements of PpIX concentration were obtained from tissue locations that were subsequently biopsied and evaluated histopathologically. Mixed models for random effects and receiver operating characteristic curve analysis for diagnostic performance were performed on the fluorescence data relative to the gold-standard histopathology. RESULTS Five of the 12 LGGs (1 ganglioglioma 1 oligoastrocytoma 1 pleomorphic xanthoastrocytoma 1 oligodendroglioma and 1 ependymoma) demonstrated at least 1 instance of visible fluorescence during surgery. Visible fluorescence evaluated on a specimen-by-specimen basis yielded a diagnostic accuracy of 38.0% (cutoff threshold: visible fluorescence score ≥ 1 area under the curve = 0.514). Quantitative fluorescence yielded a diagnostic accuracy of 67% (for a cutoff threshold of the concentration of PpIX [CPpIX] > 0.0056 μg/ml area under the curve = 0.66). The authors found that 45% (9/20) of nonvisibly fluorescent tumor specimens which would have otherwise gone undetected accumulated diagnostically significant levels of CPpIX that were detected quantitatively. CONCLUSIONS The authors’ initial Batimastat (BB-94) experience with ALA-induced PpIX fluorescence in LGGs concurs with other literature reports that the resulting visual fluorescence has poor diagnostic accuracy. However the authors also found that diagnostically significant levels of CPpIX do accumulate in LGGs and the resulting fluorescence emissions are very often below the detection threshold of current visual fluorescence imaging methods. Indeed at least in the authors’ initial experience reported here if quantitative detection methods are deployed the diagnostic performance of ALA-induced PpIX fluorescence in LGGs approaches Batimastat (BB-94) the accuracy associated with visual fluorescence in Itgb7 HGGs. Keywords: low-grade glioma fluorescence-guided surgery protoporphyrin IX 5 acid optical spectroscopy quantitative fluorescence brain tumor biomedical optics oncology Gliomas account for more than 70% of all primary brain tumors.6 Low-grade gliomas (LGGs) in particular (WHO Grades I and II) account for a variety of subtypes based on histological appearance including diffuse astrocytomas pilocytic astrocytomas oligodendrogliomas gangliogliomas and oligoastrocytomas.22 Retrospective studies of long-term data suggest that gross-total resection is associated with significantly improved progression-free Batimastat (BB-94) and overall survival within this population.18 31 33 In some instances of LGGs complete resection can even be curative in these patients. Tumor biomarkers that can be detected during intraoperative procedures hold promise for assisting and enabling further extent of resection.51 Specifically several clinical trials have considered protoporphyrin IX (PpIX)-an endogenous fluorescent biomarker that can be visually detected under violet-blue light excitation following exogenous administration of 5-aminolevulinic acid (ALA)- for fluorescence-guided resection.11 21 23 26 28 35 43 52 Importantly the use of ALA-induced PpIX has improved complete resection and has led to statistically significant increases in progression-free survival in a randomized controlled Phase III clinical trial of high-grade gliomas (HGGs).23 35 Despite these positive outcomes in HGGs early experience with ALA-induced PpIX fluorescence in LGGs has been much more negative because these tumors have not been nearly as visually fluorescent as their HGG counterparts.1 7 10 11 13 15 17 20 29 30 34 35 41 47 49 52 However the vast majority of clinical studies on fluorescence-guided neurosurgery have only considered the qualitative visible PpIX emissions. In these investigations a surgical microscope modified for fluorescence imaging is typically deployed and provides a.