MRI of Hypoxia in Primary Central Nervous System Tumors: Part I

Abstract

Hypoxia plays a key role in tumor resistance to treatment and prediction of patient prognosis in a variety of central nervous system (CNS) tumors, including glioblastoma (GBM) and meningioma. The current noninvasive imaging modalities allow for assessment of hypoxia with implications for understanding tumor biology, predicting recurrence, and aiding in treatment strategies. In part I of this review, we discuss the underlying mechanism of hypoxia in GBM and describe the use of advanced MRI to understand tumor hypoxia. In part II, we will discuss the role of positron emission tomography (PET) in assessing GBM. Importance of Hypoxia in Tumors Hypoxia is defi ned as decreased oxygen tissue perfusion below normal physiological levels, and its infl uence is at the heart of tumor biology (Figure 1). As tumors increase in size beyond 1 mm, vasculature is required to meet oxygenation requirements. Tumors that grow rapidly in size or resistance to hypoxic environments often have deranged hypoxia signaling pathways. Multiple mechanisms contribute to the development of hypoxia in CNS tumors, including high cell proliferation rates, ineffi cient neovascularization, limited oxygen diffusion, alterations of normal blood–brain barrier function, poor nitric oxide permeability, and formation of a necrotic microenvironment. Hypoxia has been implicated in the development of tumor resistance via numerous mechanisms, including reduced effi cacy of oxidative radicals critical to the function of radiotherapy and chemotherapy, impaired delivery of chemotherapy agents, dysregulation of cancer stem cells in CNS tumors, increased hematopoietic cell infi ltration and neovascularization, increased endothelial cell survival via secreted vascular endothelial growth factor (VEGF), and