19F NMR spectroscopy will be used to directly and noninvasively monitor the distribution of four fluorinated anesthetic agents (halothane, methoxyflurane, isoflurane and enflurane) in rabbit brain. The compounds selected vary in their potencies as anesthetic agents, in their solubilities in various tissues, and in the degree of their bio-transformation. The 19F signals derived from the anesthetic molecule itself will be used to detect its presence and to assess the environment(s) in which this molecule resides within the brain tissue. Using one- and two-dimensional NMR imaging techniques we plan to determine the distribution of halothane in the brain and to identify the brain structures which comprise the fast and slow brain compartments observed in our elimination studies. To achieve these objectives we plan initially to apply the existing NMR imaging techniques by adapting them to meet the requirements of our-specific problems. We will concentrate on technical developments in two areas: design of new imaging coils and pulse sequences tailored to optimize the 19F NMR imaging of anesthetics. The time-course of anesthetic uptake and elimination from the brain under well defined physiological conditions will be studied with in vivo 19F spectroscopy. To unequivically identify the origin of the observed 19F signals, the in vivo results will be supplemented during and after anesthesia is terminated. The fluorine-containing compounds will then be isolated from the tissue and identified using chromatography and NMR spectroscopy. To define the molecular environment of the anesthetic binding site(s) in brain tissue, 19F and 2H NMR studies of the anesthetic molecules will be examined. The dynamics of the binding processes will be followed with T1 and T2 relaxation time measurements.
