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Fluorescence Lifetime Imaging and Spectroscopic Co-Validation for Protoporphyrin IX-Guided Tumor Visualization in
David Reichert1,2, Mikael T Erkkilae1, Johanna Gesperger1,3
1Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria.
Frontiers in Oncology
|October 1, 2021
Summary
Fluorescence lifetime imaging enhances brain tumor surgery by distinguishing tumor tissue, even in low-grade gliomas, improving maximal safe resection. This advanced technique offers better visualization beyond standard fluorescence guidance.
Area of Science:
- Neurosurgery
- Biophotonics
- Oncology
Background:
- Maximal safe resection is crucial for brain tumor patient outcomes.
- Intraoperative fluorescence guidance using 5-aminolevulinic acid (5-ALA) is standard for high-grade gliomas but limited for low-grade gliomas due to autofluorescence.
- Fluorescence lifetime imaging (FLIM) can differentiate overlapping fluorophores, showing promise for improved tumor visualization.
Purpose of the Study:
- To integrate frequency-domain fluorescence lifetime imaging (FD-FLIM) with fluorescence spectroscopy into a surgical microscope.
- To evaluate the potential of combined FLIM and spectroscopy for distinguishing various brain tumor types and infiltration zones.
- To assess the clinical translation potential of FLIM for optimizing maximal safe resection in brain tumor surgery.
Main Methods:
- Integrated FD-FLIM with a surgical microscope and spatially registered fluorescence spectroscopy.
- Acquired fluorescence lifetime maps and spectra from ex-vivo brain tumor specimens: low-grade gliomas (n=15), high-grade gliomas (n=80), meningiomas (n=41), and metastases (n=35).
- Analyzed fluorescence lifetime changes associated with protoporphyrin IX accumulation and tissue autofluorescence in different tumor types and tissues.
Main Results:
- FLIM combined with spectroscopy successfully differentiated tumor infiltration zones and core areas in low-grade gliomas from non-pathologic tissue based on increased fluorescence lifetimes.
- Significantly increased fluorescence lifetimes were observed in infiltrated/reactive and necrotic/core areas of high-grade gliomas and metastases compared to normal tissue.
- Meningioma specimens exhibited markedly increased fluorescence lifetimes (12.2ns ± 2.5ns, p = 0.005).
Conclusions:
- Fluorescence lifetime imaging holds significant potential for enhancing maximal safe resection in brain tumor surgery.
- This technology can overcome limitations of current fluorescence guidance, particularly for low-grade gliomas and weakly infiltrated tissues.
- The study highlights the promising clinical translation of FLIM for improved intraoperative tumor detection and resection.
Keywords:
fluorescence lifetime imaging (FLIM)fluorescence spectroscopyfluorescence-guided surgeryprotoporphyrin IXsurgical microscope
