Chemical exchange saturation transfer (CEST) MRI detects myelin changes in cuprizone mouse model at 3T.

Chemical exchange saturation transfer (CEST) sensitively detects molecular alterations in the brain, such as relayed nuclear Overhauser effect (rNOE) CEST contrast at -3.5 ppm representing aliphatic protons in both lipids and proteins, and CEST contrast at 3.5 ppm correlates with protein amide protons. Myelin is rich in lipids, thus CEST could be explored as biomarkers for myelin pathology, which could contribute to multiple sclerosis (MS) diagnosis and prognosis. In this study, we aim to investigate the specificity of aliphatic rNOE and amide pool in myelin detection using cuprizone (CPZ) mouse model, which recapitulates the demyelination and remyelination of MS. In this study, preclinical 3T MRI was performed in nineteen male C57BL/6 mice. Mice in normal control group (NC, n=9) were fed with normal diet for the whole course, while mice in CPZ group (n=10) were fed with CPZ for 10 weeks followed by 4 weeks with normal diet. CEST contrasts of rNOE (-3.5 ppm) and amide (3.5 ppm) in brain regions of corpus callosum (CC) and caudate putamen were compared. Statistical differences among the groups were found with two-way ANOVA. We observed significant decreased rNOE (NC: 4.85 ± 0.09 %/s vs CPZ: 3.88 ± 0.18 %/s, p = 0.007) and amide pool (NC: 3.20 ± 0.10 %/s vs CPZ: 2.46 ± 0.16 %/s, p = 0.02) in CC after 8 weeks on CPZ diet (p < 0.05). Moreover, rNOE in CPZ recovered to a comparable level as NC at week 14 (p = 0.39), while amide remained at low level as NC (p = 0.051). Significant rNOE and amide changes validated with immunohistochemistry results of the demyelination and remyelination demonstrated great potential of CEST in revealing myelin pathology, which has implications in MS identification at the clinical-field strength 3T.