Intraoperative visualization of brain tumors with 5-aminolevulinic acid-induced fluorescence

Precise histopathological diagnosis of brain tumors is essential for the optimal patient management. Furthermore, complete resection of brain tumors is associated with an improved patient prognosis. However, histopathological undergrading and incomplete tumor removal are not uncommon, especially due to insufficient intraoperative visualization of brain tumor tissue. The fluorescent dye 5-aminolevulinic acid (5-ALA) is currently applied for fluorescence-guided resections of high-grade gliomas. The value of 5-ALA-induced protoporphyrin (PpIX) fluorescence for intraoperative visualization of other tumors than high-grade gliomas remains unclear. Within the frame of this thesis, we found a significantly higher rate of complete resections of our high-grade gliomas as compared to control cases by using the newly established 5-ALA fluorescence technology at our department. Additionally, we showed that MRI spectroscopy-based chemical shift imaging (CSI) is capable to identify intratumoral high-grade glioma areas (= anaplastic foci) during navigation-guided resections to avoid histopathological undergrading. However, the accuracy of navigation systems with integrated preoperative imaging data such as CSI declines during resections due to intraoperative brain-shift. In two further studies, we found that 5-ALA induced PpIX fluorescence is capable as a novel intraoperative marker to detect anaplastic foci within initially suspected low-grade gliomas independent of brain-shift. Finally, we showed that the application of 5-ALA is also of relevance in needle biopsies for intraoperative identification of representative brain tumor tissue. These data indicate that 5-ALA is not only of major importance for resection of high-grade gliomas, but also for intraoperative visualization of anaplastic foci as well as representative brain tumor tissue in needle biopsies unaffected by brain-shift. Consequently, this new technique might become a novel standard in brain tumor surgery that optimizes the patient management and improves the patient prognosis by maximizing the extent of tumor resection and enabling a precise histopathological tumor diagnosis.