Fluorescence-Guided Surgery in the Surgical Treatment of Gliomas: Past, Present and Future

Abstract

Gliomas are central nervous systems tumours which are diffusely infiltrative and difficult to treat. The extent of surgical resection is correlated with improved outcomes, including survival and disease-free progression. Cancerous tissue can be directly visualised intra-operatively under fluorescence by administration of 5-aminolevulinic acid to the patient. The adoption of this technique has allowed surgeons worldwide to achieve greater extents of resection, with implications for improved prognosis. However, there are practical limitations to use of 5-aminolevulinic acid. New adjuncts in the field of fluorescence-guided surgery aim to improve recognition of the interface between tumour and brain with the objective of improving resection and patient outcomes.

Rapid Intraoperative Detection of Residual Glioma Cell in Resection Cavity Walls Using a Compact Fluorescence Microscope

“…[25] Conventionally, the extent of resection of the tumor bulk evaluated the gadoliniumenhanced postoperative MRI was the most important prognostic factor. [7][8][9][10] The target of FGR using 5-ALA was the tumor bulk demonstrating the gadolinium-enhancement on MRI, and this procedure was clinically approved as improving the progression-free survival of glioblastoma patients, but did nots prolong the overall survival of these patients. [7] Therefore, in glioblastoma surgery, as much as possible of the surrounding tissues infiltrated by tumor cells should be resected, up to the boundary of the functional region of the brain.…”

“…[7] Therefore, in glioblastoma surgery, as much as possible of the surrounding tissues infiltrated by tumor cells should be resected, up to the boundary of the functional region of the brain. [8][9][10]25] Recently, the significance of aiming at the "supra-total" resection, which is resection of tissue containing the invading glioblastoma cells in the area demonstrating a high signal on the preoperative FLAIR imaging beyond the gadolinium-enhanced tumor bulk was reported. [5] However, the subjective evaluation of fluorescence emission by the naked eye, the problems with the sensitivity and specificity of PPIX accumulation within tumor cells, and the autofluorescence of PPIX from normal brain tissue were important clinical issue in performing the FGR using 5-ALA, particularly for additional resection of the region demonstrating "vague" fluorescence around the tumor bulk emitting strong fluorescence.…”

“…[5] However, the subjective evaluation of fluorescence emission by the naked eye, the problems with the sensitivity and specificity of PPIX accumulation within tumor cells, and the autofluorescence of PPIX from normal brain tissue were important clinical issue in performing the FGR using 5-ALA, particularly for additional resection of the region demonstrating "vague" fluorescence around the tumor bulk emitting strong fluorescence. [8][9][10][11][12][13][14][15] There have numerous discussions regarding these unresolved problems to date.…”

“…[1][2][3][4][5][6] Recently, the surgical usefulness of the fluorescence-guided resection (FGR) method using the photosensitizer, 5-aminolevulinic acid (5-ALA) has been accepted worldwide, and neurosurgeons confront the malignant gliomas with this novel intraoperative method to improve the extent of resection of these tumors. [7][8][9] However, with the spread of the FGR method, its problems and limitations have become clear, such as the problem of specificity of 5-ALA accumulation in tumor cells, and the problem of the subjective assessment of the intensity of fluorescence by the surgeon's naked eyes under the surgical microscope. [9][10] Therefore, basic and clinical studies on quantification of the 5-ALA metabolite protoporphyrin IX (PPIX) in the brain and tumor tissues using optical spectroscopy have been performed, and intraoperative augmentation methods of this information using artificial intelligence have been developed to overcome these problems and limitations of FGR.…”

“…[7][8][9] However, with the spread of the FGR method, its problems and limitations have become clear, such as the problem of specificity of 5-ALA accumulation in tumor cells, and the problem of the subjective assessment of the intensity of fluorescence by the surgeon's naked eyes under the surgical microscope. [9][10] Therefore, basic and clinical studies on quantification of the 5-ALA metabolite protoporphyrin IX (PPIX) in the brain and tumor tissues using optical spectroscopy have been performed, and intraoperative augmentation methods of this information using artificial intelligence have been developed to overcome these problems and limitations of FGR. [11][12][13][14][15] We have been investigating the possibilities of performing the FGR method using another photosensitizer, talaporfin sodium (TPS), for malignant gliomas, and reported the selective accumulation of TPS in glioma cells in both in vitro and in vivo studies, and developed an intraoperative photodiagnosis method using TPS with semiconductor laser systems.…”