Label-Free Macroscopic Fluorescence Lifetime Imaging of Brain Tumors

Abstract

Advanced stage glioma is the most aggressive form of malignant brain tumors with a short survival time. Real-time pathology assisted, or image guided surgical procedures that eliminate tumors promise to improve the clinical outcome and prolong the lives of patients. Our work is focused on the development of a rapid and sensitive assay for intraoperative diagnostics of glioma and identification of optical markers essential for differentiation between tumors and healthy brain tissues. We utilized fluorescence lifetime imaging (FLIM) of endogenous fluorophores related to metabolism of the glioma from freshly excised brains tissues. Macroscopic time-resolved fluorescence images of three intracranial animal glioma models and surgical samples of patients’ glioblastoma together with the white matter have been collected. Several established and new algorithms were applied to identify the imaging markers of the tumors. We found that fluorescence lifetime parameters characteristic of the glioma provided background for differentiation between the tumors and intact brain tissues. All three rat tumor models demonstrated substantial differences between the malignant and normal tissue. Similarly, tumors from patients demonstrated statistically significant differences from the peritumoral white matter without infiltration. While the data and the analysis presented in this paper are preliminary and further investigation with a larger number of samples is required, the proposed approach based on the macroscopic FLIM has a high potential for diagnostics of glioma and evaluation of the surgical margins of gliomas.

Fluorescence Lifetime Imaging and Spectroscopic Co-Validation for Protoporphyrin IX-Guided Tumor Visualization in Neurosurgery

“…Alfonso-Garcia et al intraoperatively demonstrated increased lifetimes for necrotic tissue respective to cortex as well as decreased lifetimes for an oligodendroglioma patient when comparing to the lifetimes of adjacent white matter (54). Higher mean NADH fluorescence lifetimes were also observed in glioblastomas respective to physiological brain (27,55). The interested reader is also referred to Marcu and Hartl (25).…”

Raman Imaging and Fluorescence Lifetime Imaging Microscopy for Diagnosis of Cancer State and Metabolic Monitoring

“…For the broad clinical implementation of FLIM, application in large samples is particularly necessary. Here, wide-field FLIM and recent advances in establishing macroscopic FLIM imaging have been achieved, allowing the scanning of whole tissue samples [ 142 , 261 ].…”

Near-Infrared Inorganic Nanomaterials for Precise Diagnosis and Therapy

“…Nanoparticles doped with appropriate lanthanide ions has proved to enhance NIR emission through energy trapping or suppress the up-conversion pathway ( Chen et al, 2017 ; Zhong et al, 2017 ). Fluorescence lifetime as a new dimension become highly useful in multichannel bioimaging ( Figure 2D ), which are independent of both colour and intensity ( Laviv et al, 2016 ; Fan et al, 2018 ; Zheng et al, 2018 ; Xie et al, 2020 ; Lukina et al, 2021 ; Luo et al, 2021 ). Zhang group designed NIR-II RENPs with tunable luminescence lifetimes for in vivo quantitative imaging ( Fan et al, 2018 ).…”