Molecular and cellular investigation of rodent brains by magnetic resonance imaging

Abstract

Magnetic Resonance Imaging (MRI) is a non-ionizing imaging modality that can provide images with excellent soft tissue contrast at high resolution. In particular, molecular and cellular MRI is a powerful imaging method that could provide a non-invasive way for assessing specific biological processes in vivo in living organisms. The ability to monitor and track biological structures and processes down to molecular and cellular level and the possibility to probe the development, survival, migration, and differentiation of cells in vivo, has opened up new ways for scientists to investigate the fundamental mechanisms of health and diseases. In this dissertation, novel applications of conventional MR contrast agents to study specific biological structures and processes are demonstrated. First, the potential of manganese enhanced MRI (MEMRI) for in vivo tract tracing and assessment of neuroarchitecture was investigated. Manganese was intracortically infused into the visual cortex along the border of the primary and secondary visual cortex and then imaged 8 and 24 hours later. A dynamic migratory path of manganese from the infusion site through the corpus callosum to the contralateral hemisphere was observed. Also, layer specific enhancement on the contralateral cortex and the connection of the visual cortex with other brain structures were shown and the results were consistent with established anatomical data. Secondly, MEMRI was performed to probe in vivo neuronal changes in the rodent brain following 72-hour rapid eye movement sleep deprivation. Significant reduction in manganese uptake was observed in the cortical and hippocampal region in the sleep deprived animals when compared to the normal group. In particular, the dentate gyrus substructure in the hippocampus exhibited the least uptake. This indicated the functional vulnerability of the hippocampus and the cortex to sleep deprivation. Lastly, in vivo tracking of endogenous neural stem and progenitor cell migration during neurogenesis in neonatal rat brain was performed by micron sized iron oxide particles (MPIO) labeling. Susceptibility weighted imaging was used for image processing to highlight the susceptibility contrast induced by the iron oxide particles. MPIO-labeled cells induced contrast was clearly enhanced in the susceptibility weighted images, particularly at day 3 after MPIO injection in which the MPIO-labeled NPCs became more dispersed in the olfactory bulb. The ventral migratory pathway of endogenous neural stem and progenitor cells, which could not be easily observed in conventional T2*W imaging, couldalsobe detected. Overall, various biological systems and processes have been successfully interrogated using MR contrast agents. Through these studies, the versatility and power of molecular and cellular MRI have been demonstrated. Looking ahead, the rapid development and combination of different molecular and cellular imaging techniques would certainly revolutionize the way we study health and diseases. In the end, this could foster our understanding of basic life sciences and hence improve the quality of healthcare.