The overall goal of this work is to develop functional magnetic resonance imaging (MRI) and optical imaging techniques that allow non-invasive assessment of brain and heart function. MRI technqiues are having a broad impact on understanding brain. Anatomical based MRI has been very useful for separating gray and white matter and detecting numerous brain disorders. Functional MRI techniques enable detection of regions of the brain that are active during a task. Molecular MRI is an emerging area, whose major goal is to image a large variety of processes in tissues. Our goal is to impact MRI developments in all these areas. Over the past year we have demonstrated that manganese chloride gives MRI contrast that defines neural architecture. In particular, twenty four hours after systemic administration we can detect layers in olfactory bulb, cerebellum and cortex. We have assigned the cortical layers detected using manganese enhanced MRI by comparison to histology. Over the past couple of years, we have completed studies in the rodent brain that acquired very high temporal and spatial resolution functional MRI to monitor changes in hemodynamics during forepaw stimulation. The results clearly indicate that specific layers in the mammalian cortex can be defined. To test if fMRI is detecting laminar communication, specific protocols that rely on well known inhibitory circuits have been developed. We have demonstrated that the pattern of fMRI activation is altered in these inhibitory paradigms opening up the possibility of using fMRI to distinguish """"""""bottom up"""""""" inputs into an area from """"""""top down"""""""" inputs. We have extended fMRI of the rodent to enable whole brain coverage. This technique is being used to study plasticity due to peripheral nerve damage and changes in the brain due to associative learning tasks. Preliminary results indicate that fMRI of the rodent brain will be able to detect changes associated with learning and plasticity and be useful to study these processes. We have continued to develop the use of manganese ion and micron sized iron oxide particles as molecular and cellular MRI contrast agents. Previously we have shown that manganese ion can sensitize MRI to assess calcium influx and to trace neuronal connections in vivo. Over the past year we have developed a protocol that enables us to trace the neural representation of a specific odor from the olfactory neurons in the nose to specific glomeruli in the olfacotry bulb. Furthermore, preliminary results indicate that we will be able to trace this representation to the mitral cell layer in the bulb. The ability to trace specific active represnetations through the brain is a unique feature of manganese enhanced MRI. Finally, we have been successful at detecting single cells migrating in the brain and to the liver using micron sized iron oxide particles. These are very potent MRI contrast agents that have enbaled us to label endogenous neural stem cells in the subventricular zone and then detect migration of these cells to the olfactory bulb. The ability to track these cells in the same animal that we can perform fucntional MRI and manganese based neural tracing should give us a unique view of the rodent brain during plasticity and learning.
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