Metal Doped Iron Oxide Nanomaterials As High-Performance Magnetic Resonance Imaging Contrast Agents

The relaxation rates are low and the sensitivity need to be improved for current magnetic resonance imaging(MRI)contrast agents in clinical use.Therefore,it is of great significance to develop high-performance contrast agents for accurate imaging and diagnosis in tissues.Magnetic iron oxide nanoparticles as the one of the most widely developed contrast agents in the field,however,the study ont the relationships of their crystal structures and magnetic properties are very preliminary.How to effectively improve their contrast abilities still requires in-depth development.This thesis is based on the nanostructure of iron oxide and comprehensively investigates the structure-activity nexus of metal doping,size,morphology and their contrast ability.These methods greatly improve the sensitivity of imaging and the accuracy of diagnostic analysis in contrast-enhanced MRI.In Chapter 1,we briefly introduced the research background of MRI technology,the imaging principle of MRI and three types of MRI contrast agents.We also proposed several possible strategies to design high-performance contrast agents for MRI.In Chapter 2,we reported a facile synthesis of europium-engineered iron oxide(EuIO)nanocubes as T1 and T2 contrast agents for MRI in living subjects.The accuracy and reliability of imaging or diagnosis are significantly improved compared to those contrast agents with single model.The Eu(?)oxide-embedded iron oxide nanoparticles significantly increase the T1 relaxivity with an enhanced positive contrast effect.EuIO nanocubes with 14 nm in diameter showed a high r1 value of 36.8mM-1s-1 with respect to total metal ions(Fe + Eu),which is about 3 times higher than that of Fe3O4 nanoparticles with similar size.Moreover,both r1 and r2 values of EuIO nanocubes can be tuned by varying their sizes and Eu doping ratios.After citrate coating,EuIO nanocubes can provide enhanced T1 and T2 contrast effects in small animals,particularly in the cardiac and liver regions.This work may provide an insightful strategy to design MRI contrast agents with both positive and negative contrast abilities for biomedical applications.In Chapter 3,we explored the effects of manganese doping on ferrite crystal structures,magnetic properties and contrast abilities.We synthesized a high-performance T2 contrast agent by optimizing the manganese doping level.Interestingly,the saturation magnetization and T2 contrast ability of ferrite nanoparticles increase along with rising manganese proportions,peak when the doping level reaches x = 0.43,while decrease dramatically as the manganese percentage continues to augment.At high manganese doping level,the manganese ferrite nanoparticles may undergo lattice distortion,which may result in low saturation magnetization and eventually low T2 contrast ability.On the other hand,as the manganese doping level increases,partial Mn2+ ions may occupy tetrahedral sites(Td)rather than octahedral sites(Oh)of the inverse spinel structure of magnetite,which leads to partial cancellation of the net magnetic moments.This work also opens a new field of vision for developing high-performance T2 contrast agents by modulating the metal composition of nanoparticles.In Chapter 4,we investigated the mechanism of how morphology influences the water proton relaxation process with the optimum manganese doping ratio model described in the third chapter.We synthesized manganese-doped iron oxide(MnIO)nanoparticles with six types of different shapes but the same geometrical volume and investigated the relationship between morphologies and T1/T2 relaxation rates.The morphology of magnetic nanoparticles largely determined the effective radii and the gradient of stray fields induced by nanoparticles,which affect the transverse relaxation rates.In the longitudinal relaxation process,T1 relaxivities have positive correlation with surface to volume ratio and the occupancy rate of metal ions on exposed surfaces of magnetic nanoparticles.The relationship between morphology and relaxivity and the summary of r2/r1 ratios can guide to screen the optimal shapes for promising T1 or T2 contrast agents.The effective radius can serve as a rule to obtain high negative contrast abilities.The surface to volume ratio and exposed surface are helpful to design T1 positive contrast agents.These principles would become guidelines for development of high-performance contrast agents in the field of MRI.In Chapter 5,we developed the zinc doped iron oxide octapods as high-performance T2 contrast agent on the basis of the octapods structure in the fourth chapter.The nanoparticles have ultrahigh transverse relaxation rate and T2 contrast ability due to their large effective radius and the optimum zinc doping proportion.In vivo liver and in situ carcinoma contrast-enhanced imaging both showed excellent T2 contrast effect.This work is helpful to develop potential magnetic resonance contrast agents with high sensitivity and low doses and low side effects.