| Summary: | 碩士 === 國立中山大學 === 化學系研究所 === 104 === Magnetic resonance imaging (MRI) has become the most important non-invasive method for providing three dimensional detailed images without using damaging radiation and is a powerful tool in materials science, biomedicine, medical diagnosis, food science and many other fields. In many situations such as in disease detection, however, the image contrast is not sufficient. Therefore, through the MRI contrast agent, its high paramagnetic ion can effectively and selectively accelerate water 1H nuclear relaxation rates. Therefore, water molecules in different microenvironments obtain a different relaxation acceleration so that a better contrast is achieved for the diseased regions.
However, current theory for MRI contrast agent was developed by assuming that the paramagnetic ions are located in a dilute aqueous solution. This is a good approximation in many situations such as water in a relatively free microenvironments, but cellular environment is highly crowded with various kinds of biomacromolecules (proteins, hydrocarbonates, genetic materials etc), small molecules (hormones, vitamins etc) and ions (H+, Na+, K+, Cl- etc). The performance of MRI contrast agent may be significantly altered by crowders and ions. Understanding how the contrast agent interacts with other molecules in cell is a very important and challenging problem.
In this work, we focus on the influence of common ions in organisms and macromolecular crowding effect on the performance of MRI contrast agent. The MRI contrast agent we chose is Dotarem which is the mostly used in medical diagnosis.. Then we follow the standard practice of selecting a macromolecular crowder (polyethylene glycol, M.W. 6000, PEG6k, an artificial inert macromolecule, with no specific structure in aqueous solutions) to mimic cellular environment. The ions used here are those mostly commonly found in humans (LiCl, NaCl, KCl, MgCl2, CaCl2, NaI). 1H NMR relaxation rates and translational diffusion rate of water and PEG6k are measured on a 500 MHz NMR spectrometer equipped with a Pulse Filed Gradient (PFG) unit. It is found that the longitudinal relaxation rates and translational diffusion coefficient are sensitive measures for quantifying the effects of ions and macromolecular crowders on the performance of MRI contrast agent. Within the concentration range typically present in an organism, these dynamic parameters are found to clearly depend on the concentration, type and valence number of the ions besides the concentration of MRI contrast agent and macromolecular crowding effect. These results are further supplemented by fast field cycling relaxometry (NMR relaxation dispersion) over a range between 0.01 – 40 MHz. The physical chemistry mechanism of these effects is elucidated by analyzing the experimental results. The significance of these effects to practical MRI is discussed. Based on the experimental and theoretical results as well as the analysis, we conclude that both the ionic and macromolecular effects must be taken into account for more precise MRI diagnosis or functional MRI studies.
|
|---|
