Laser-induced fluorescence: experimental intraoperative delineation of tumor resection margins

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Abstract
The ability of laser-induced fluorescence spectroscopy to delineate tumor margins intraoperatively was studied using a rat intracerebral glioma model. A fluorescent dye, chloro-aluminum phthalocyanine tetrasulfonate (ClAlPcS4), was injected intravenously 24 hours before tumor resection. The animals underwent tumor resection under the operating microscope, guided by laser-induced fluorescence measurement in one group (Group 1) and visual assessment in the other (Group 2). The Group 1 rats had a significantly reduced volume of residual tumor following resection (0.5 +/- 0.2 cu mm vs. 13.7 +/- 4.0 cu mm, mean +/- standard error of the mean, p less than 0.02). Three of the nine animals in Group 1 were tumor-free at 2 weeks following resection, compared with none of the 10 rats in Group 2 (p less than 0.05). Interference from brain autofluorescence was minimized using spectrally resolved detection and the ClAlPcS4 dye, which has a 680-nm fluorescence peak significantly higher than the 470-nm autofluorescence peak of normal brain. Contrast ratios of up to 40:1 were found for glioma:normal brain fluorescence signals. Spatially-resolved spectra were acquired in approximately 5 seconds using a fiberoptic probe. This study demonstrates the ability of an intraoperative laser-induced fluorescence system to detect tumor margins that could not be identified with the operating microscope.