Three-dimensional morphometric analysis: quantifying the infiltrative growth of astrocytomas in animal model

Abstract

Widespread brain infiltration is a hallmark of malignant brain tumors. Particularly in the case of glioblastomas (GBM) - the most common and aggressive type of brain tumors in adults -, despite maximal initial tumor resection and multimodality therapy, 90% of GBM patients will experience disease recurrence within few years of treatment, mainly due to their aggressive invasiveness into the brain. Biologically, despite of significant advances in the understanding of the mutational events and signaling pathways that drive GBM progression, many aspects of their invasive nature are still not fully understood. This is due to the fact that brain invasive process is very complex and difficult to study experimentally in a fully controlled way. Indeed, an understanding of the patterns of GBM invasion in the complex brain microenvironment is essential to a more integrated view of GBM biology. In this case, the use of living models is mandatory. In collaboration with Dr. Stephan Preibisch, a computational biologist and group leader with extensive experience in current state-of-the art of light microscopy and complex image analysis, we aim to study the patterns of glioblastoma invasion in relation to the brain microenvironment by using 3D microscopic imaging in transparent brain. The use of fluorescent xenotransplanted GBM tumor cells and optically cleared, transparent mice brains will permit the high-resolution imaging and quantification of invasive patterns of human GBM cells into mice brains. Our results will supplement the usual 2D histology or others laborious methods that reconstructs small brain volumes and partially represent glioma tumor morphology. (AU)