Abstract
Precise intraoperative brain tumor visualization supports surgeons in achieving maximal safe resection. In this sense, improved prognosis in patients with high-grade gliomas undergoing protoporphyrin IX fluorescence-guided surgery has been demonstrated. Phase fluorescence lifetime imaging in the frequency-domain has shown promise to distinguish weak protoporphyrin IX fluorescence from competing endogenous tissue fluorophores, thus allowing for brain tumor detection with high sensitivity. In this work, we show that this technique can be further improved by minimizing the crosstalk of autofluorescence signal contributions when only detecting the fluorescence emission above 615 nm. Combining fluorescence lifetime and spectroscopic measurements on a set of 130 ex vivo brain tumor specimens (14 low- and 56 high-grade gliomas, 39 meningiomas and 21 metastases) coherently substantiated the resulting increase of the fluorescence lifetime with respect to the detection band employed in previous work. This is of major interest for obtaining a clear-cut distinction from the autofluorescence background of the physiological brain. In particular, the median fluorescence lifetime of low- and high-grade glioma specimens lacking visual fluorescence during surgical resection was increased from 4.7 ns to 5.4 ns and 2.9 ns to 3.3 ns, respectively. While more data are needed to create statistical evidence, the coherence of what was observed throughout all tumor groups emphasized that this optimization should be taken into account for future studies.
Highlights
We hypothesize that adjusting the spectral detection band to optimize the Protoporphyrin IX (PpIX) to autofluorescence ratio further increases the overall measured lifetime, enhancing the contrast to the autofluorescence background of physiological brain parenchyma. Both FD-FLIM and spectroscopic fluorescence data were acquired ex vivo on a set of 130 brain tumor specimens. We evaluated both FD-FLIM and combined time- and spectrally resolved fluorescence data to verify the adjustments made to the detection band
When detecting weak PpIX concentrations in fluorescence-guided surgery, the autofluorescence background of the brain can be stronger than the actual PpIX fluorescence
We improved FD-FLIM PpIX visualization for fluorescence-guided surgery by minimizing autofluorescence crosstalk within the detection band
Summary
Maximizing the extent of resection while prioritizing neurological function in cytoreductive surgery is one of the most decisive prognostic factors and essential in the initial treatment of gliomas, meningiomas (MNG) and brain metastases (MET) [3,4,5,6,7,8,9]. Protoporphyrin IX (PpIX) fluorescence guidance was first established for intraoperative visualization of high-grade gliomas (HGG) [10,11] and was afterwards investigated in MNG [12] and MET [13], with promising results. Presurgical administration of the non-fluorescent precursor 5-aminolevulinic acid (5-ALA) leads to tumor-specific metabolization of PpIX [14]. Surgical microscopes can be equipped with optical filters to visualize the red fluorescence of PpIX and thereby detect tumorous tissue.
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