Magnetic Resonance Microscopy of a Glioma Spheriod in a Collagen I Matrix

Introduction: Amongst their distinct characteristics, human high-grade gliomas, particularly glioblastomas, exhibit not only rapid volumetric growth dynamics but also extensive local infiltration into the adjacent brain parenchyma. It is this characteristic local cell invasion that renders these tumors surgically non-curable and motivates ongoing research to better understand the crucial relationship between tumor and its microenvironment. Employing a multicellular tumor spheroid (MTS) model that focuses on glioma MTS evolving within extracellular matrix environments, we have previously investigated the spatio-temporal expansion dynamics in vitro [Refs ] and have started to model them in silico [Refs ]. However, relevance for and applicability of the insights gained from these intriguing interdisciplinary studies to the clinical area will also depend on evidence that the experimental system can be analyzed with methods and techniques that are utilized in clinics as well. As such, NMR-techniques, that currently build the backbone of clinical neuro-imaging, will have to be employed and the results have to be compared with light and fluorescence microscopy methods that are commonly used to monitor MTS growth and invasion in vitro. Here, we have applied magnetic resonance microscopy (MRM) to the glioma MTS model and were able to show that MRM can easily distinguish a multicellular tumor spheroid of roughly 250 μm in diameter in a collagen I matrix, even in the absence of any labeling. It is therefore feasible to use MRM to monitor tumor cell expansion in vitro at a resolution comparable to light microscopy.