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. T 2 -weighted imaging, B 1 field mapping, and CEST imaging under four B 1 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. B 1 inhomogeneity was corrected using a smoothing spline interpolation algorithm. pH-sensitive CrCEST ratiometric was measured by dividing CrCEST under B 1 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.
Background Medical imaging modalities, such as magnetic resonance imaging (MRI), ultrasound, and fluorescence imaging, have gained widespread acceptance in clinical practice for tumor diagnosis. Each imaging modality has its own unique principles, advantages, and limitations, thus necessitating a multimodal approach for a comprehensive disease understanding of the disease process. To enhance diagnostic precision, physicians frequently integrate data from multiple imaging modalities, driving research advancements in multimodal imaging technology research.Methods In this study, hematoporphyrin-poly (lactic acid) (HP-PLLA) polymer was prepared via ring-opening polymerization and thoroughly characterized using FT-IR, 1H-NMR, XRD, and TGA. HP-PLLA based nanoparticles encapsulating perfluoropentane (PFP) and salicylic acid were prepared via emulsion-solvent evaporation. Zeta potential and mean diameter were assessed using DLS and TEM. Biocompatibility was evaluated via cell migration, hemolysis, and cytotoxicity assays. Ultrasonic imaging was performed with a dedicated apparatus, while CEST MRI was conducted using a 7.0 T animal scanner.Results We designed and prepared a novel dual-mode nanoimaging probe SA/PFP@HP-PLLA NPs. PFP enhanced US imaging, while salicylic acid bolstered CEST imaging. With an average size of 74.43 ± 1.12 nm, a polydispersity index of 0.175 ± 0.015, and a surface zeta potential of −64.1 ± 2.11 mV. These NPs exhibit excellent biocompatibility and stability. Both in vitro and in vivo experiments confirmed the SA/PFP@HP-PLLA NP’s ability to improve tumor characterization and diagnostic precision.Conclusion The SA/PFP@HP-PLLA NPs demonstrate promising dual-modality imaging capabilities, indicating their potential for preclinical and clinical use as a contrast agent.
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