Measurement of regional perfusion is critical for the understanding of a variety of physiological and pathological processes. Availability of a technique for this measurement that is non-invasive, provides excellent spatial resolution and is suitable for repeated, serial measurements would be of considerable importance. Recent advances in NMR imaging have generated a number of possible methods for measuring cerebral perfusion, many of which fulfill some or all of these criteria. Remarkably, despite the enormous potential of these NMR techniques, none has yet been fully developed or rigorously validated in vivo against a widely-accepted measurement of regional organ perfusion. We propose to develop and validate two NMR methods of measurement of regional cerebral perfusion for potential use in humans. The first employs 2H2O as a freely-diffusible tracer and the second relies on spin-echo amplitude attenuation caused by movement of protons (1H2O) in a magnetic field gradient. The 2H2O tracer method will first be developed with single-voxel experiments in rats. The signal-to-noise and measurement-time constraints related to the use of various sites for tracer administration will be determined and evaluated with both washin and washout kinetic protocols. Rigorous validation of the measurements will be carried out by concomitant measurements employing the radiolabeled microsphere technique. In order to develop the 1H spin-echo technique for quantitative, single- voxel perfusion measurements in rat, a high-performance, linear z-axis gradient and compatible homogeneous-excitation, surface-coil-receive probe will be constructed. The assumptions underlying the method will be limitations of the techniques. It will then be validated against concomitant flow measurement in rat by the radiolabeled microsphere technique. Both techniques will then be extended to multi-voxel experiments (perfusion imaging) in cats with development of the necessary probe and gradient hardware for interrogation of cat brain. The limitations for measurement time, spatial resolution and precision will be determined. Again, measurements made with both methods will be compared with concomitant measurements by the radiolabeled microsphere technique. In the final phase, a sufficient number of studies will be performed on monkeys, whose size is similar to that of human neonates, to further assess the suitability of these techniques for use in humans.
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