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To evaluate between-site agreement of apparent diffusion coefficient (ADC) measurements in preclinical magnetic resonance imaging (MRI) systems.A miniaturized thermally stable ice-water phantom was devised. ADC (mean and interquartile range) was measured over several days, on 4.7T, 7T, and 9.4T Bruker, Agilent, and Magnex small-animal MRI systems using a common protocol across seven sites. Day-to-day repeatability was expressed as percent variation of mean ADC between acquisitions. Cross-site reproducibility was expressed as 1.96 × standard deviation of percent deviation of ADC values.ADC measurements were equivalent across all seven sites with a cross-site ADC reproducibility of 6.3%. Mean day-to-day repeatability of ADC measurements was 2.3%, and no site was identified as presenting different measurements than others (analysis of variance [ANOVA] P = 0.02, post-hoc test n.s.). Between-slice ADC variability was negligible and similar between sites (P = 0.15). Mean within-region-of-interest ADC variability was 5.5%, with one site presenting a significantly greater variation than the others (P = 0.0013).Absolute ADC values in preclinical studies are comparable between sites and equipment, provided standardized protocols are employed.

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 (ADCz) of 0.76 ± 0.06 × 10−3 mm2/s, similar to the contralateral tissue and significantly smaller than untreated gliomas (0.97 ± 0.13 × 10−3 mm2/s). They had higher perfusion rates (66 ± 4 mL/100 g·min) than untreated gliomas (26 ± 7 mL/100 g·min). 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. J. Magn. Reson. Imaging 2010;31:796–806. ©2010 Wiley-Liss, Inc.

butyl nitrone(PBN), on glioma-affected neuronal fibers. The fiber trac-tography method was able to differentiate between differenttumor types, such as the C6 and F98 rat glioma models.MaterialsandMethods:C6orF98cellswereintracraniallyinjected into the cortex of male Fischer 344 rats. PBN treat-ment was initiated before or after cell implantation. Tumorgrowth was monitored with diffusion tensor imaging (DTI)and fiber tractography using diffusion-weighting gradientsin 30 noncolinear directions.Results: Although proton density-weighted (PDw) and T2-weighted (T2w) images did not show any difference betweenC6 and F98 gliomas without edema, the apparent diffusioncoefficient (ADC) and fractional anisotropy (FA) maps wereable to discriminate between these two tumor models. Fibertractography was used to visualize C6 glioma-induced isch-emia of tumor-surrounding tissues, whereas F98 gliomawas found to infiltrate and penetrate into the corpus callo-sum (CC). During glioma growth, neuronal fibers werefound to disappear at the border regions between the tumorand surrounding tissues. PBN treatment was shown toinhibit glioma growth with accompanying changes in thesurrounding tissue.Conclusion: By noninvasively monitoring the degree ofneuronal fiber integrity and connectivity with the use ofneuronal fiber tractography, we were able to evaluate theprotective effect of PBN against invasive glioma growth inrat brains. PBN provided protection of the neuronal fibersagainst tumor-induced ischemia and tumor invasion.Key Words: MRI; diffusion tensor imaging; fiber tractogra-phy; neuronal fiber; glioma; C6 glioma cell; F98 glioma cell;antioxidant; free radical; phenyl