F-19 NUCLEAR-MAGNETIC-RESONANCE IMAGING AND SPECTROSCOPY OF SEVOFLURANE UPTAKE, DISTRIBUTION, AND ELIMINATION IN RAT-BRAIN

Background: Determination of macroscopic and microscopic distribution of general anesthetics can facilitate identification of anatomic, cell ular, and molecular loci of anesthetic action. Previous attempts to me asure brain anesthetic distributions with fluorine-19 (F-19) nuclear m agnetic resonance (NMR) imaging were conducted at magnetic field stren gths lower than 2 Tesla. All have produced only silhouettes of brain t issue. Difficulties intrinsic to NMR imaging of anesthetics include hi gher anesthetic solubility in extracranial tissues and the lower limit s to spin-echo delay times that can be used in conventional NMR imagin g methods. So far, such methods have been unable to capture rapidly de caying brain F-19 NMR signals. Methods: F-19 NMR imaging and spectrosc opy were conducted at 4.7 Tesla using a specially developed NMR probe and new imaging methods, With the new techniques, it was possible to o bserve directly the uptake, distribution, and elimination in brain of sevoflurane, a fluorinated general anesthetic with special advantages for NMR investigations. Results: F-19 NMR images, acquired at differen t times after sevoflurane administration, clearly showed the distribut ion of a fluorinated general anesthetic within the brain. Based on con tinuous transverse relaxation time measurements, sevoflurane signals c ould be separated into two components, attributable respectively to se voflurane in a mobile or immobile microenvironment. During washin, the re was a delayed accumulation of anesthetic in the mobile microenviron ment. During washout, there was a rapid elimination from the immobile microenvironment. Conclusions: At anesthetizing concentrations, sevofl urane distributes heterogeneously in the brain. Sevoflurane in the bra in tissue contributes mostly to the immobile component of the F-19 sig nal, whereas that in the surrounding adipose and muscle tissues contri butes mostly to the mobile component. Imaging and spectroscopic result s suggest that the immobile component of sevoflurane is associated wit h the general anesthetic effects of the agent.