The brain primarily relies on glucose as the energy source for its metabolism. Traditionally, 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) scan was the imaging method for studying the glucose metabolism in the brain. In recent years, a chemical exchange saturation transfer (CEST) method using the proton exchange between glucose and water as a contrast mechanism has been proposed to investigate dynamic glucose enhancement (DGE). DGE can be used to understand the dynamic metabolism of glucose over time. However, most applications of CEST imaging involve only the CEST-induced changes in the image to locate lesions. Only a few studies are focusing on the connection between metabolites and disease mechanisms. The goal of this study is to improve and utilize CEST imaging to investigate the metabolic dynamics and accumulation status of glucose in the brain of mice with tumors and Huntington’s disease (HD). Based on the results of CEST imaging, pathological, and biochemical approaches will be used to explore the underlying mechanisms during disease progression in HD mice. Also, a simulation model of glucose metabolism in the brain is applied to explain the DGE data. The CEST imaging approach is expected to provide a more effective, inexpensive, and non-invasive diagnostic method for studying neurodegenerative diseases.