Functional assessment of glioma pathogenesis by in vivo multi-parametric magnetic resonance imaging and in vitro analyses

Gliomas are aggressive brain tumors with poor prognosis and remain refractory to treatment. The purpose of this dissertation is providing a novel approach combining in vivo multi-parametric magnetic resonance imaging (MRI) and immunohistochemistry, with the assistance of in vitro cell culture assessments, to monitor the pathogenic development of gliomas. Three inter-related studies are included in this dissertation. The first part is to use osteopontin (OPN) as a model molecule to establish functional assessment of glioma pathogenesis using multi-parametric MRI combined with in vitro analyses, which can be further applied to assess the functional roles of other driver genes in promoting cancer hallmarks related to proliferation, angiogenesis and altered metabolism. In the second study, the multi-parametric MRI methods were performed to demonstrate the role of host microenvironment in dictating the aggressiveness of gliomas, through differential programming of tumor-associated macrophages. We show that the differential polarization of glioma-associated macrophages (GAMs) into M1 or M2 subtypes in different host microenvironments is associated with aggressive phenotypes of gliomas, suggesting that macrophage programming plays an important role in glioma development and that targeting GAMs may serve as a promising therapeutic approach. The third part is to combine T2-weighted MRI and immunohistochemical analyses to evaluate the effects of targeted migration of neural stem/progenitor cells (NSPCs) on tumor development in N-ethyl-N-nitrosourea (ENU)-induced rat brain tumor model.