Utility of spectroscopic quantitative evaluation of 5-aminolevulinic acid fluorescence for maximizing resection in meningioma surgery

Abstract Background Few studies have examined the utility of 5-ALA-photodynamic diagnosis (PDD) in meningioma surgery. We aimed to investigate how 5-ALA-PDD is applied to meningioma surgery using fluorescence spectroscopy for quantitative evaluation. To explore the molecular mechanisms by which meningiomas can display fluorescence of protoporphyrin IX (PpIX), gene expressions related to PpIX metabolism were also analyzed. Methods Participants comprised 35 patients with meningioma who underwent surgical resection using 5-ALA-PDD. After confirming that no tumor remained in the resectable area, remaining tumor cells were visualized by 5-ALA-PDD. Laser-diode spectroscopy was used to evaluate the 5-ALA fluorescence intensity of tumor cells invading surrounding tissues. The proliferation of tumor cells in those tissues was assessed by immunohistochemistry for Ki-67. Gene expression profiles were also examined in last 11 patients by RNA sequencing. Results All meningiomas displayed PpIX fluorescence of different intensities, with 22 patients requiring additional resection of tumor cells. The tumor core showed high median fluorescence intensity. PpIX fluorescence intensity correlated significantly with Ki-67 staining index (SI). Ki-67 SI values in areas showing fluorescence intensity over 10,000 a.u. were significantly greater than those in areas presenting fluorescence intensity under 10,000 a.u. RNA sequencing analysis disclosed reduced expressions of factors in meningiomas related to PpIX metabolism, including IDH-1, ALAS-1, FECH and ABCG2. Conclusions Tumor with fluorescence intensity exceeding 10,000 a.u. might be considered for resection as completely as possible. When planning meningioma surgery, 5-ALA-PDD with a spectroscopic device could be useful for fluorescence-guided surgery and for indicating tumor cells invading tumor-adjacent normal tissues.