Abstract
Abstract
BACKGROUND
Fluorescence guidance with 5-aminolevulinic acid(5-ALA) increases resection extent and may benefit surgical outcomes in high-grade gliomas. We investigated if a combination of various fluorescence guidance techniques can provide further advantage. We systematically assessed and compared the fluorescent patterns of 5-ALA-induced protoporphyrin IX (PpIX), fluorescein sodium(FNa) and indocyanine green(ICG) to identify GL261 gliomas in mice and RFP-U251 gliomas in rats.
METHODS
5-ALA(5mg), FNa(5 mg/kg) and ICG(20mg/kg) were administered perioperatively. Fluorescence patterns were recorded with operative microscope, laser scanning confocal microscope, and confocal laser endomicroscope. Fluorescence was assessed quantitatively as a surface area of fluorescent positive tissue and qualitatively(false/true, positive/negative) as compared to HE-stained histology.
RESULTS
FNa highlighted a larger surface area(18.0mm2) than white light(16.9mm2,p=0.016) or PpIX (16.0mm2,p=0.035). Both 5-ALA and FNa showed inhomogeneous staining patterns: multiple areas of equal staining, when PpIX was present and FNa was not, and vice versa. ICG was visible in 8/31 tumor samples, all immediately after injection. ICG did not reveal clear tumor margins, but stained non-tumor tissue and nearby vasculature. FNa signal was stronger (tumor to background ratio (TBR)1.93 ± 0.56) compared to 5-ALA(1.52 ± 0.31;p
CONCLUSION
ICG highlighted tumor only within the first few minutes and stained mostly hypervascularized areas. Confocal and surgical imaging revealed inhomogeneous tumor border staining with PpIX/FNa. Simultaneous administration of 5-ALA and FNA may provide additional benefit. Neither ICG, 5-ALA or FNa worked perfectly, emphasizing the need for more specific markers for fluorescence-guided brain tumor resection.