**5. MRI methods to detect gliomas**

Magnetic resonance imaging (MRI) techniques are becoming more commonly used to provide information on brain tumor growth, vasculature, biochemical metabolism, and molecular changes in preclinical models, as MRI is the optimal imaging tool as part of the diagnostic process for human gliomas. Conventional MRI techniques, such as T1- and T2 weighted imaging, contrast-enhanced T1-weighted imaging, dynamic contrast enhanced (DCE) imaging, and diffusion-weighted imaging (DWI) methods can provide useful information on tumor location and extent of growth, blood-brain barrier (BBB) disruption, brain invasiveness, regional blood flow and blood volume, and tumor cellularity, all of which are characteristics associated with glioma grade and prognosis in a clinical setting (Waerzeggers *et al*., 2010).

Morphological MRI (T2-weighted or T1-weighted contrast-enhanced imaging) is used to provide information on tumor volumes and growth rates, which can be used to distinguish between tumor grades. Contrast-enhanced imaging can be used to assesses BBB disruption, however this feature can be absent in diffuse infiltrative tumor regions or when assessing therapeutic treatment (Waerzeggers *et al*., 2010). DCE imaging can be used to follow tumor angiogenesis by measuring changes in tumor vascular permeability, vascular density and vessel morphology (Waerzeggers *et al*., 2010), particularly regarding the capillary bed. Magnetic resonance angiography (MRA) is also used to provide information on tumor vasculature associated with angiogenesis, however it tends to be restricted to major blood vessels >50 microns in diameter (Doblas *et al*., 2010). DWI has been used in cancer imaging to evaluate tumor cellularity and infiltration, as well as monitor therapeutic response (Kauppinen, 2002). Metabolic information can be obtained by monitoring tumor metabolites by a method called MR spectroscopy (MRS), or variations thereof, such as MR spectroscopic imaging (MRSI) or chemical shift imaging (CSI). Molecular alterations can be assessed with the use of targeting MR contrast agents which can specifically indicate levels of cancer biomarkers that may be elevated in malignant tumors. The development of targeted imaging ligands attached to MRI contrast agents allows the *in vivo* evaluation of tumor biology, such as tumor cell apoptosis, angiogenic blood vessels or the expression of specific tumor antigens or signaling pathways (Waerzeggers *et al*., 2010).
