Purpose: To evaluate the added value of non-contrastenhanced MR angiography (MRA) to conventional MR imaging for a detailed characterization of different rodent glioma models. Materials and Methods:Intracerebral tumor cell implantation and chemical induction methods were implemented to obtain rat C6, 9L/LacZ, F98, RG2, and ethyl-nitrosourea (ENU) -induced glioma models, a human U87 MG tumor model as well as a mouse GL261 glioma model. MR assessments were regularly conducted on a 7 Tesla Bruker BioSpin system. The tumor border sharpness and growth characteristics of each glioma model were assessed from T 2 -weighted images. Neovascularization and vascular alterations inherent to each model were characterized by assessing absolute blood volumes, vessel density, length, and diameter using Mathematica and Amira software.Results: The 9L/LacZ and ENU gliomas both presented flaws that hinder their use as reliable brain tumor models. C6 gliomas were slightly invasive and induced moderate vascular alterations, whereas GL261 tumors dramatically altered the brain vessels in the glioma region. F98, RG2, and U87 are infiltrative models that produced dramatic vascular alterations.Conclusion: MRI and MRA provided crucial in vivo information to identify a distinctive ''fingerprint'' for each of our seven rodent glioma models.

Purpose: To demonstrate that OKN007, a disulfonyl derivative of phenyl-tert-butyl nitrone (PBN), has anti-glioma activity in the clinically relevant C6 rat glioma model using multi-parametric magnetic resonance imaging.Materials and Methods: Twenty-one rats were intracerebrally implanted with C6 cells and administered OKN007 or kept as controls. Animals were monitored with MRI at 7 Tesla (T), using morphologic, diffusion-weighted and perfusion imaging, followed by histology and Western blots of angiogenesis and inflammatory markers.Results: OKN007 was found to decrease tumor volumes and increase survival. The glioma tissues of OKN007-treated rats were found to have longitudinal apparent diffusion coefficients (ADC z ) of 0.76 6 0.06 Â 10 À3 mm 2 /s, similar to the contralateral tissue and significantly smaller than untreated gliomas (0.97 6 0.13 Â 10 À3 mm 2 /s). They had higher perfusion rates (66 6 4 mL/100 gÁmin) than untreated gliomas (26 6 7 mL/100 gÁmin). All examined molecular markers were decreased in OKN007-treated rat gliomas, compared with elevated levels in untreated rats.Conclusion: MRI assessment was successfully used to monitor a decrease in tumor growth, and corresponding alterations in ADC and perfusion rates in rat C6 gliomas treated with the anti-glioma agent, OKN007.

Assessment of metabolites by 1H MRS could provide information regarding glioma growth, and perhaps distinguish between different glioma models. Rat C6, 9L/LacZ, F98 or RG2, or mouse GL261 cells were intracerebrally implanted into respective rodents, and human U87 MG cells were implanted into athymic rats. Ethyl-nitrosourea (ENU) induction was also used. Glioma metabolites (e.g. total choline (tCho), total creatine (tCr), N-acetyl-aspartate (NAA), lactate (Lac), glutamine (Gln), glutamate (Glu), aspartate (Asp), guanosine (Gua), mobile lipids, and macromolecules (MM)) were assessed from 1H MRS with PRESS (TE, 24 ms, TR, 2500 ms, and VAPOR water suppression; 27 μl or 8 μl voxels in rats or mice, respectively) at 7 Tesla. Alterations in metabolites (TARQUIN) in tumors, were characterized by increases in lipids (Lip1.3; 8.8–54.5 mM for C6 and GL261) and decreases in NAA (1.3–2.0 mM for RG2, GL261 and C6) and tCr (0.8–4.0 mM in F98, RG2, GL261 and C6) in some models. F98, RG2, GL261 and C6 models all had significantly decreased (p<0.05) tCr, and RG2, GL261 and C6 had significantly decreased (p<0.05) NAA. The RG2 model had significantly decreased (p<0.05) Gln and Glu, the C6 model had significantly decreased (p<0.05) Asp, and the F98 and U87 models had significantly decreased (p<0.05) Gua, compared to controls. GL261 had the greatest alterations in metabolites. 1H MRS was able to differentiate metabolic profiles in many of the 7 rodent glioma models assessed. These models are considered to resemble some characteristics of human glioblastomas, and this study may be helpful in selecting appropriate models.