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Probing demyelination and remyelination of the cuprizone mouse model using multimodality MRI
Nian Wang1,2, Jie Zhuang2, Hongjiang Wei2
1Center for in vivo Microscopy, Duke University, Durham, North Carolina, USA.
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.
Insights
Quantitative susceptibility mapping (QSM) effectively detects demyelination in mice models. This MRI technique shows high sensitivity and variation in white matter, complementing traditional methods for studying neurological conditions.
Area of Science:
- Neuroimaging and neuroscience research.
- Investigating demyelination and remyelination processes in the central nervous system.
Background:
- The corpus callosum (CC) is highly susceptible to demyelination induced by cuprizone.
- Current MRI methods for detecting demyelination and remyelination are limited.
Purpose of the Study:
- To evaluate the sensitivity of multiparametric MRI for detecting demyelination and remyelination.
- To assess both in vivo and ex vivo MRI techniques in a cuprizone-induced demyelination model.
Main Methods:
- Utilized a cuprizone mouse model with control and varying exposure groups.
- Employed advanced MRI sequences including 3D GRE, T2-weighted imaging, and diffusion tensor imaging (DTI) at high field strengths (7.0T and 9.4T).
- Assessed DTI metrics, quantitative susceptibility mapping (QSM), and T2-weighted imaging intensity in white matter.
Main Results:
- In vivo and ex vivo susceptibility values significantly increased in the CC and anterior commissure (AC) after cuprizone exposure.
- Susceptibility values demonstrated high sensitivity to demyelination, with greater variation than radial diffusivity in ex vivo studies.
- Voxel-based analysis revealed differential susceptibility variations across white matter tracts and intraregional demyelination.
Conclusions:
- Quantitative susceptibility mapping (QSM) is highly sensitive to the demyelination process induced by cuprizone.
- QSM serves as a valuable complementary technique to conventional T2-weighted imaging and DTI metrics for assessing demyelination.
- Multiparametric MRI, particularly QSM, offers robust in vivo and ex vivo detection of demyelination and remyelination.
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