Optical Imaging at the Microscopic Scale: 5-ALA-derived Brain Tumor Fluorescence for Fluorescence-Guided Resections

Glioblastoma is the most frequent and the most aggressive primitive brain tumour in adults. Prognosis remains poor with 5-year survival rates of only 5%. Maximal safe surgical resection, which is the gold standard as first-line therapy, is a major prognostic factor. To improve the onco-functional balance, it is mandatory to protect the healthy brain tissue while maximizing the resection of tumor tissue. However, current image-based surgical tools (MRI, neuronavigation, and ultrasonography) do not allow to accurately distinguish tumor tissue from healthy brain tissue. In this context, the intraoperative induced fluorescence has been developed. The preoperative injection of a fluorescent dye - the 5-aminolevulinic acid - to the patients with a glioblastoma allows locating intraoperatively the glioma cells, which preferentially absorb the dye and became fluorescent after an appropriate light excitation. The intraoperative induced fluorescence can already be used in current neurosurgical clinical practice using an operating microscope specially equipped: it increases both the extent of resection and the progression-free survival, as a consequence. However, this macroscopic detection has a limited spatial resolution. So, various neurosurgical groups, particularly those of the Barrow Institute (Phoenix, USA) and of the Pierre-Wertheimer Hospital (Lyon, France), develop high-resolution detection devices of the intraoperative induced fluorescence with confocal microscopy. Their preliminary studies highlight the possibility to detect glioma cells at the cell spatial scale, in real time during surgical resection. The optical imaging can improve the management of patients harboring a glioblastoma, leading to a better and safer surgical resection and improving both the survival and the quality of life of these patients.