The objectives of this project are to develop MRI techniques for monitoring of brain function. This work was begun by development of a perfusion MRI technique that relies on arterial spin labeling of endogenous water as a perfusion tracer. Over the past five years, this class of perfusion MRI technique has been established as useful for measuring regional blood flow in the brain during rest, task activation, and in disease states in both humans and animal models. This technique makes quantitative measurements of regional blood flow with the spatial and temporal resolution of MRI in a variety of tissues. Further development of this class of techniques is being carried out with experiments designed to extend strategies for arterial spin labeling, make use of the labeled water as a probe of water extraction into tissue, and make it routine to acquire rapid three dimensional images in the mouse brain. Furthermore, when applied to the brain, this class of perfusion imaging technique should be useful for brain mapping studies and, in particular, forms a complement to BOLD techniques. Presently, all functional MRI techniques monitor the hemodynamic consequences of neuronal activation rather than a direct effect of neuronal activity. The cascade of events that lead to neuronal activation are release of neurotransmitter, depolarization, influx of calcium, release of neurotransmitter, and so on. Hemodynamic changes occur as a response of the brain to maintain homeostasis. A more direct MRI measure of neuronal activation might be very useful. Preliminary results indicate that Mn2~ might be an excellent contrast agent to probe calcium influx associated with neuronal activity in animal models. In addition, Mn2~ appears to act as an anterograde neuronal tracer once it enters neurons. Both of these exciting results open the possibility of extending functional MR techniques for the brain.
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