5-aminolevulinic acid (5-ALA) is routinely used in neurosurgery to enhance visualization of glioblastoma multiforme (GBM) and enable more extensive tumor resection. However, intraoperative guidance based solely on 5-ALA–induced protoporphyrin IX (PpIX) fluorescence remains limited by qualitative interpretation, low sensitivity, and insufficient specificity for detecting tumor infiltration at surgical margins - regions critical for minimizing recurrence. Recent studies suggest that brain tissue autofluorescence (AF), which reflects biochemical composition and metabolic state, may provide complementary diagnostic information to PpIX and that could improve margin detection. This study investigates whether fluorescence lifetime (FLT) measurements of PpIX, supplemented by FLT of brain tissue autofluorescence, improve detection of tumor infiltration at the resection margin in patients in vivo . Using a mesoscopic fiber-based multispectral fluorescence lifetime imaging (FLIm) device with 355 nm excitation, we simultaneously acquire time-resolved emission from AF channels (390/40 nm and 470/28 nm) and PpIX fluorescence (629/52 nm) in 15 patients with IDH-wild-type GBM, evaluating a total of 86 surgical margins during craniotomy procedures. Logistic regression analysis applied to all available FLIm-derived parameters identified FLT at 390 nm and FLT at 629 nm (PpIX) as the optimal features for tumor detection, achieving an area under the curve (AUC) of 0.85. These results demonstrate that FLT of combined brain AF and PpIX significantly improves sensitivity over conventional visual assessment, highlighting its potential as a quantitative approach to enhance surgical precision and patient outcomes.
Adams et al. (Mon,) studied this question.