Probing demyelination and remyelination of the cuprizone mouse model using multimodality MRI

Abstract

Background Various studies by MRI exhibit that the corpus callosum (CC) is the most vulnerable to cuprizone administration, detecting the demyelination and remyelination process using different MRI parameters are, however, lacking. Purpose To investigate the sensitivity of multiparametric MRI both in vivo and ex vivo for demyelination and remyelination. Study Type Prospective. Animal Model A cuprizone mice model with an age‐matched control group (n = 5), 4‐week cuprizone exposure group followed by 9‐week on a normal diet (n = 6), and a 13‐week cuprizone exposure group (n = 6). Field Strength/Sequence 3D gradient recalled echo, T2‐weighted, and diffusion tensor imaging (DTI) at 7.0T and 9.4T. Assessment Quantification of DTI metrics, quantitative susceptibility mapping (QSM), and T2‐weighted imaging intensity in major white matter bundles. Statistical Tests Nonparametric permutation tests were used with a cluster‐forming threshold as 3.09 (equivalent to P = 0.001), and the significant level as P = 0.05 with family‐wise correction. Results In vivo susceptibility values increased from –11.7 to –0.7 ppb (P < 0.001) in CC and from –13.7 to –5.1 ppb (P < 0.001) in the anterior commissure (AC) after the 13‐week cuprizone exposure. Ex vivo susceptibility values increased from –25.4 to 7.4 ppb (P < 0.001) in CC and from –41.6 to –15.8 ppb (P < 0.001) in AC. Susceptibility values showed high variations to demyelination for in vivo studies (94.0% in CC, 62.8% in AC). Susceptibility values exhibited higher variations than radial diffusivity for ex vivo studies (129.1% vs. 28.3% in CC, 62.0% vs. 25.0% in AC). In addition to the differential susceptibility variations in different white matter tracts, intraregional demyelination variation was also present not only in CC but also in the AC area by voxel‐based analysis. Data Conclusion QSM is sensitive to the demyelination process of cuprizone exposure, which can be a complementary technique to conventional T2‐weighted images and DTI metrics. Level of Evidence: 2 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019;50:1852–1865.

A roadmap of brain recovery in a mouse model of concussion: insights from neuroimaging

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Temporal Changes in In Vivo Glutamate Signal during Demyelination and Remyelination in the Corpus Callosum: A Glutamate-Weighted Chemical Exchange Saturation Transfer Imaging Study

“…Starting at four weeks of age, 18 male Sprague–Dawley rats were obtained from Orient Bio, Inc. (Seongnam, Kyunggi-do, Korea) and divided into the cuprizone-administered ( n = 12) and normal control (CTRL, n = 6) groups. All twelve treatment rats were fed a milled diet containing 0.2% cuprizone (bis[cyclohexanone]oxaldihydrazone; Sigma–Aldrich, St. Louis, MO, USA), ad libitum , for seven weeks to induce demyelination [ 15 , 20 , 28 ]. Among the twelve rats, two died during cuprizone administration, so the demyelination and remyelination groups consisted of five rats each.…”