Two-peaked 5-ALA-induced PpIX fluorescence emission spectrum distinguishes glioblastomas from low grade gliomas and infiltrative component of glioblastomas - PubMed (original) (raw)

Two-peaked 5-ALA-induced PpIX fluorescence emission spectrum distinguishes glioblastomas from low grade gliomas and infiltrative component of glioblastomas

Bruno Montcel et al. Biomed Opt Express. 2013.

Abstract

5-ALA-induced protoporphyrin IX (PpIX) fluorescence enables to guiding in intra-operative surgical glioma resection. However at present, it has yet to be shown that this method is able to identify infiltrative component of glioma. In extracted tumor tissues we measured a two-peaked emission in low grade gliomas and in the infiltrative component of glioblastomas due to multiple photochemical states of PpIX. The second emission peak appearing at 620 nm (shifted by 14 nm from the main peak at 634 nm) limits the sensibility of current methods to measured PpIX concentration. We propose new measured parameters, by taking into consideration the two-peaked emission, to overcome these limitations in sensitivity. These parameters clearly distinguish the solid component of glioblastomas from low grade gliomas and infiltrative component of glioblastomas.

Keywords: (000.1430) Biology and medicine; (170.4580) Optical diagnostics for medicine; (170.6280) Spectroscopy, fluorescence and luminescence; (170.6510) Spectroscopy, tissue diagnostics.

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Figures

Fig. 1

Fig. 1

Simulated and in vitro calibration experiments. (a) PpIX emission spectra measured in vitro for the two physicochemical states with peak wavelength at 634 nm (blue dotted line) and 620 nm (red dashed line) and for photoproducts (brown dashed and dotted line). (b, c) Two examples of fitting of PpIX emission spectra in vitro (solutions at ratio620/634 = 0.98 (b) and ratio620/634 = 0.38 (c)), measured (x signs), simulated (green solid line), fitted[PpIX634]η634I634λ (blue dotted line), fitted [PpIX620]η620I620λ (red dashed line) and fitted photoproducts (brown dashed and dotted line).

Fig. 2

Fig. 2

Simulated and in vitro calibration experiments. (a) Influence of the microenvironment on ratio620/634. (b) Fitted PpIX fluorescence intensities of [PpIX634]η634 ( + signs), [PpIX620]η620 (o signs) and photoproducts (* signs) in function of ratio620/634.

Fig. 3

Fig. 3

Extracted tumor tissues experiments. (a) Extraction of auto-fluorescence in measured spectrum, example of a measured spectrum (x signs) and exponential decay fitting of auto-fluorescence (solid line). (b) Example of fitting of PpIX emission spectrum on an extracted tumor tissues (ratio620/634 = 0.56), measured (x signs), simulated (green solid line), fitted [PpIX634]η634I634λ (blue dotted line), fitted [PpIX620]η620I620λ (red dashed line) and fitted photoproducts (brown dashed and dotted line).

Fig. 4

Fig. 4

Extracted tumor tissues experiments statistical tests. (a) ratio620/634, (b) fitted [PpIX634]η634 and (c) fitted [PpIX620]η620 for the 4 groups GBMst (n = 5), GBMinf (n = 16), Gst (n = 7) and Ginf (n = 7). Mean (grey column) and standard error of the mean are shown (error bar). *P < 0.05, **P < 0.01, ***P < 0.001. Two sample Kolmogorov-Smirnov test.

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