Glucose-weighted CEST MRI in Adipose Tissue and Sepsis induced AKI

Abstract

CEST is an advanced MRI technique that is widely used today in both clinical and research. In particular, glucoCEST can be alternative to the contrast enhancement MRI technique using gadolinium (M. Kim et al., 2022). In the scope of this thesis, the CEST and glucoCEST techniques are applied to two main topics: FAT and S-AKI. Within the FAT topic, two subtopics are explored: characterizing different types of adipose tissue and evaluating glucose uptake in BAT under both resting and activated conditions. For the S-AKI topic, glucoCEST is used to assess it as a promising biomarker. This experiment is conducted in several phases: in-vitro, ex-vivo, and then transferred to in-vivo. Sections 1 and 2 provide an overview of the research direction and the fundamental principles, including MRI physics, the principles of CEST, and glucoCEST. Section 3 focuses on the characterization of adipose tissue, while Section 4 evaluates the effectiveness of the glucoCEST technique in assessing the 6-hour S-AKI model. The first project aims to differentiate between BAT and WAT using CEST spectra, with glucose as a tracer to distinguish between the two. Additionally, it evaluates the potential of the glucoCEST technique to detect the activation status of BAT through a pharmacological activation method. In this project, based on the CEST spectrum, we have clearly distinguished between the spectra of WAT and BAT based on the characteristic structure of this type of adipose tissue. In Part 2 of the first project, the glucoCEST technique was applied with two infusion methods, i.v. and i.p., to observe the different absorption times of BAT with glucose. The i.v. method showed faster wash-in and wash-out compared to the i.p. method. This shows the reasonableness of applying the i.v technique for the BAT activation experiment because the drug activation time only lasts from 40-60 minutes after injection. In addition, ex-vivo experiments with the combination of activation drugs showed the ability of the glucoCEST technique to detect BAT before and after activation. It shows the potential of glucoCEST to evaluate the function of BAT. <br/> The second project shows the results of the experiment applying the glucoCEST technique to evaluate S-AKI. We used a S-AKI mice model that was generated by PCI model. The results of kidney injury were confirmed by the change of some blood index such as creatine, HDL and urea. MRI assessments were performed 6h after S-AKI, including the application of D-GLC, 3-OMG as a contrast agent, T₁ mapping, and T₂ mapping. The results of glucoCEST showed that there was a change in signal between the control group and S-AKI in both types of glucose injection. The change was also observed in the T₂ mapping results between healthy and disease groups. In contrast, the T₁ mapping in the injured kidneys did not show a significant change compared with the healthy group. Additionally, the T₂ values changed in the control group before and after injection, particularly in the pelvis region. This suggests that glucose injection alters the properties of urine. This finding aligns with the AACID results, where similar changes were observed in the pelvis, indicating a shift in the pH environment after glucose injection. <br/> Our results show that glucoCEST MRI is more sensitive to the change in septic groups in the early time point at 20 minutes. It indicates that glucoCEST can be a potential biomarker to evaluate the early stage of S-AKI.