Analysis of PpIX in suspected low-grade gliomas

1.) Title of the project: Quantitative measurement of 5-aminolevulinic acid (5-ALA) induced protoporphyrin IX accumulation to optimize surgery of suspected low-grade gliomas 2.) Content of the project: In the present project, we will use a newly developed intraoperative probe that is based on fluorescence technology. This probe is capable to visualize specific brain tumors and their tumor margin that are usually hardly visible during tumor removal. Furthermore, this surgical adjunct will support the neurosurgeon to detect tumor areas with focal malignancy that remain undetected by conventionally applied intraoperative tools. 3.) Hypotheses of the project: It is hypothesized that this new probe facilitates the intraoperative detection of suspected so called low-grade gliomas. Thereby, the neurosurgeon is able to achieve a complete tumor resection. Furthermore, this probe is able to identify tumor areas with focal malignancy in order to enable a correct tumor diagnosis and thus optimal patient treatment. 4.) Methodology of the project: We will recruit a large series of patients scheduled for resection of a radiologically suspected low-grade glioma and will perform tumor resection with assistance of the intraoperative probe. During tumor resection, tissue samples will be collected from different intratumoral areas for histopathological analysis. The value of the probe for precise detection of the tumor margin as well as tumor areas with focal malignancy will be analysed. 5.) Originality of the project: Intraoperative identification of brain tumors by a specific probe represents a promising and new approach that will overcome the current drawbacks of intraoperative tools for tumor visualisation. Thus, we expect that this approach will optimize glioma surgery and therefore significantly improve the prognosis of patients with suspected low-grade gliomas.

The prognosis of patients with suspected low-grade gliomas depends mainly on the extent of neurosurgical tumor removal. However, due to the poor delineation of such brain tumors during surgery, incomplete tumor resections are very common. In recent years, it has been shown that the rapidly growing, high-grade gliomas can be visualized by visible fluorescence after oral administration of a fluorescent dye during surgery and thus the extent of tumor removal can be significantly improved. Unfortunately, there is usually no visible fluorescence in the slow-growing, low-grade gliomas, and thus this technique is currently unable to improve the demarcation of tumor tissue from healthy brain in these tumors. Recently, innovative probes have been introduced that are able to analyze the fluorescence in tumor cells and thus it is hoped that in future also primarily non-fluorescent tumors can be intraoperatively identified. At the Dartmouth-Hitchcock Medical Center (USA), a handheld probe has been developed that can also be used in neurosurgical procedures. A collaborative study with the Dartmouth-Hitchcock Medical Center allowed the possibility to conduct a clinical study at the Department of Neurosurgery, University of California, San Francisco (UCSF) to analyze the value of such a probe in a larger number of patients with radiologically suspected low-grade gliomas. As supervisor of this study served the chief of the department Prof. Mitchel S. Berger. The first results of this study as part of this international cooperation project look promising. However, a detailed analysis of the collected data has to be awaited. There is thus great hope that the mostly non-fluorescent low-grade gliomas can be better visualized during tumor removal. Thus, this innovative technique could result in a more radical resection of such tumors, thereby significantly improving the prognosis of these patients in the future.