UC Berkeley

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.