In vivo characterization of the human glioblastoma infiltrative edge with label-free intraoperative fluorescence lifetime imaging

Abstract

Challenges in identifying a glioblastoma’s infiltrative edge during neurosurgical procedures result in rapid recurrence. A label-free fluorescence lifetime imaging (FLIm) device was used to evaluate glioblastoma’s infiltrative edge in vivo in 15 patients (89 samples). FLIm data were analyzed according to tumor cell density, infiltrating tissue type (gray and white matter), and diagnosis history (new or recurrent). Infiltrations in white matter from new glioblastomas showed decreasing lifetimes and a spectral red shift with increasing tumor cell density. Areas of high versus low tumor cell density were separated through a linear discriminant analysis with a ROC-AUC=0.74. Current results support the feasibility of intraoperative FLIm for real-time in vivo brain measurements and encourage refinement to predict glioblastoma infiltrative edge, underscoring the ability of FLIm to optimize neurosurgical outcomes.

Metabolic heterogeneity of colorectal cancer as a prognostic factor: insights gained from fluorescence lifetime imaging

“…An assessment of metabolic heterogeneity in patients’ tumors seems valuable from a clinical point of view. The great efforts to translate FLIM in the clinical setting both in vivo and ex vivo have been done by several groups (Jo et al, 2018; Alfonso-Garcia et al, 2023; Weyers et al, 2022; Seidenari et al, 2012; Mycek et al, 1998; Herrando et al, 2024; Lagarto et al, 2020). Clinical translation is spearheaded through macroscopic implementation and point-spectroscopy approaches that are capable of large sampling areas and enable access to otherwise constrained spaces but lack cellular resolution, making the interpretation of the results a complicated task.…”

5-ALA induced PpIX fluorescence spectroscopy in neurosurgery: a review

“…Thus, fluorescence lifetime approaches provide an additional mechanism of optical contrast by taking advantage of differences in the tumor tissue microenvironment on the detected fluorophores. For example, and beyond the scope of this review, the literature on fluorescence lifetime measurements of endogenous markers such as NAD(P)H and flavin in gliomas is abundant, providing an alternative way of evaluating the tissue environment and photoactivity ( Stummer et al, 1998b ; Yong et al, 2006 ; Butte et al, 2010 , 2011 ; Stummer et al, 2014 ; Stummer, 2015 ; Kaneko and Kaneko, 2016 ; Kittle et al, 2016 ; Mehidine et al, 2019 ; Lukina et al, 2021 ; Alfonso-Garcia et al, 2023 ). More recently, articles on autofluorescence lifetime spectroscopy coupled with PpIX lifetime spectroscopy have also been described as a means of fluorescence-based tumor contrast ( Mehidine et al, 2019 ; Erkkilä et al, 2020 ; Reichert et al, 2021 ; Alfonso-García et al, 2022 ).…”