Amide Proton Transfer-weighted 7-T MRI Contrast of Myelination after Cuprizone Administration

Background Investigations of amide proton signal changes in the white matter of demyelinating diseases may provide important biophysical information for diagnostic and prognostic assessments. Purpose To evaluate amide proton signals in cuprizone-induced rats using amide proton transfer-weighted (APT_w) MRI, which provides in vivo image contrast by changing amide proton concentrations during demyelination (DEM) and subsequent remyelination (REM). Materials and Methods In this animal study, APT_w 7-T MRI was performed in 21 male Wistar rats divided into cuprizone-induced (n = 14) and control (n = 7) groups from February to August 2020. The cuprizone-induced group was further subdivided into DEM (n = 7) and REM (n = 7) groups. Seven weeks after cuprizone feeding, rats in the DEM group were killed prior to transmission electron microscopy and myelin staining, while rats in the REM group were changed to a normal chow diet and fed for 5 weeks. In each group, the APT_w signals were calculated using a conventional magnetization transfer ratio at 3.5 ppm based on regions of interest in the corpus callosum. Statistical differences in APT_w signals among the groups were analyzed with one-way analysis of variance followed by Tukey post hoc tests. Results The mean APT_w signals in the control and DEM groups were -4.42% ± 0.60 (standard deviation) (95% CI: -4.98, -3.86) and -2.57% ± 0.48 (95% CI: -3.01, -2.12), respectively, indicating higher in vivo APT_w signals in the DEM lesion (P < .001). After REM, mean APT_w signal in the REM group was -3.83% ± 0.67 (95% CI: -4.45, -3.22), similar to that in the control group (P = .18) and lower than that in the DEM group (P < .001). Conclusion Significant amide proton transfer-weighted (APT_w) metric changes coupled with the histologic characteristics of the demyelination and remyelination processes indicate the potential usefulness of APT_w 7-T MRI to monitor earlier myelination processes. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by van Zijl in this issue.