Intraoperative detection ofIDH‐mutant glioma using fluorescence lifetime imaging

Abstract

Identifying isocitrate dehydrogenase (IDH)-mutation and glioma subtype during surgery instead of days later can aid in modifying tumor resection strategies for better survival outcomes. We report intraoperative identification of IDHmutant glioma (N = 12 patients) with a clinically compatible fluorescence lifetime imaging (FLIm) device (excitation: 355 nm; emission spectral bands: 390/40 nm, 470/28 nm, 542/50 nm). The fluorescence-derived parameters were analyzed to study the optical contrast between IDH-mutant tumors and surrounding brain tissue. IDH-mutant oligodendrogliomas exhibited shorter lifetimes (3.3 ± 0.1 ns) than IDH-mutant astrocytomas (4.1 ± 0.1 ns). Both IDH-mutant glioma subtypes had shorter lifetimes than white matter (4.6 ± 0.4 ns) but had comparable lifetimes to cortex. Lifetimes also increased with malignancy grade within IDH-mutant oligodendrogliomas (grade 2: 2.96 ± 0.08 ns, grade 3: 3.4 ± 0.3 ns) but not within IDH-mutant astrocytomas. The current results support the feasibility of FLIm as a surgical adjuvant for identifying IDH-mutant glioma tissue.

Intraoperative molecular imaging: 3rd biennial clinical trials update

“… 72 Dr. Marcu also reported leverage of this technology to distinguish oligodendroglioma from astrocytoma indicating that label-free FLIM could be a biomarker for low-grade IDH-mutant tumors. 73 Preliminary results suggested that FLIM data can provide optical contrast between areas of high and low tumor density thereby detecting the infiltrative edge of GBM in real-time. Dr. Marcu also describes quantitative assessment of PpiX fluorescence at room light using FLIM as an augmented visualization tool for real-time resection under standard surgical field illumination.…”

“…demonstrated safe and real-time intraoperative FLIM acquisition which was correlated to histology and MRI to resolve distinct brain tissue types that were clinically relevant 72 . Dr. Marcu also reported leverage of this technology to distinguish oligodendroglioma from astrocytoma indicating that label-free FLIM could be a biomarker for low-grade IDH-mutant tumors 73 . Preliminary results suggested that FLIM data can provide optical contrast between areas of high and low tumor density thereby detecting the infiltrative edge of GBM in real-time.…”

Intraoperative detection of IDH-mutant glioma subtype using fluorescence lifetime imaging

“…The contents of the SPIE presentation at Photonics West 2023 on which this manuscript is based on has been published in the Journal of Biophotonics. 19 This study was supported by the National Institutes of Health (R01CA250512, R21CA178578), the University of California, Davis, and the Comprehensive Cancer Center's Brain Malignancies Innovation Group funded through the Comprehensive Cancer Center Support Grant (P30CA093373). The authors would also like to acknowledge the use of gramm library 20 in MATLAB for generating the figures.…”