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.
Highlights
Glioblastoma (Grade IV) is the most common and most aggressive form of malignant brain tumors with an overall survival of 14–15 months after complete surgical resection and adjuvant radiochemotherapy [1]
Tyrosine, various porphyrins, collagen and lipopigments are present in brain tissue contributing to the autofluorescence [28, 29]
The attempts to evaluate whether the fluorescence lifetime of endogenous fluorophores, can be used to distinguish between healthy brain and brain tumors have been made in several previous studies [10, 28,29,30,31,32]
Summary
Glioblastoma (Grade IV) is the most common and most aggressive form of malignant brain tumors with an overall survival of 14–15 months after complete surgical resection and adjuvant radiochemotherapy [1]. Since the extent of removal of pathological tissue defines, to a large degree, a prognosis of the disease, an accurate identification of the tumor margin during resection is crucially important [2]. Intraoperative fluorescence guidance with 5aminolevulinic acid (5-ALA) that induces protoporphyrin IX fluorescence or exogenous contrast agents (e.g. sodium fluorescein or indocyanine green) has proven to be a useful technique to improve the resection, but the challenges associated with nonspecific distribution of the fluorophore, timing and the subjective assessment of fluorescence still remain [3]. The use of 5ALA in most cases does not allow to detect low grade gliomas, it seems to be possible based on the fluorescence lifetime information [4]. Stain-free techniques that do not require sample staining is a preferable way for tumor identification
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