Investigation of Energy Metabolism Alterations in Diabetic Muscles Using CEST MRI at 5 T

Diabetes mellitus (DM) causes skeletal muscle damage. Energy metabolism alterations in diabetic muscles remain to be elucidated. Chemical exchange saturation transfer (CEST) MRI is increasingly adopted in imaging muscle energy metabolism. This study aimed to investigate energy metabolism alterations in diabetic muscles using CEST MRI. Six adult New Zealand rabbits with alloxan-induced DM were scanned on a 5 T MR imager before and 2, 4, 6, and 8 weeks after the DM model induction, with six normal rabbits as controls. T₂-weighted imaging, B₁ field mapping, and CEST imaging under four B₁ amplitudes of 0.75, 1.0, 1.25, and 1.5 μT were performed, respectively. Blood glucose level was measured before each MRI experiment. Inverse magnetization transfer ratio analysis was adopted to quantify CEST effects of two energy metabolites of creatine (Cr) and phosphocreatine (PCr), from which their ratio was calculated. B₁ inhomogeneity was corrected using a smoothing spline interpolation algorithm. pH-sensitive CrCEST ratiometric was measured by dividing CrCEST under B₁ of 1.25 μT with that under 0.75 μT. Paired student's t-test and one-way ANOVA were conducted with p < 0.05 considered statistically significant. Blood glucose level measurements confirmed the successfully induced DM model. The controls showed no significant changes in Cr- and PCr-weighted CEST signals throughout the study. In contrast, a significant increase of Cr-weighted CEST signals started in 2 weeks (p = 0.049) and became more pronounced in Week 6 (p = 0.045) and Week 8 (p = 0.002) after the DM model induction, whereas PCr-weighted CEST signals remained constant among multiple time points, leading to significantly reduced PCr/Cr in Week 6 (p = 0.047) and Week 8 (p = 0.011). Meanwhile, CrCEST ratio did not show significant alterations (p > 0.05). The significantly increased Cr-weighted CEST and reduced PCr/Cr with time implied disrupted energy metabolism in diabetic muscles, providing supplementary information for better understanding of DM-related muscle impairments from the metabolic level.