General anesthetics modify many processes important to nerve cell function. Knowledge of anesthesia-induced alterations in brain events will help in the understanding of the mechanism underlying anesthetic action. Effects of anesthesia on cerebral hemodynamics and cerebral metabolism will be assessed noninvasively by MR imaging and spectroscopy. A comprehensive multinuclear magnetic resonance project is proposed to study the influence of five fluorinated general anesthetics - halothane, isoflurane, desflurane and sevoflurane - on rabbit brain in vivo.

The 19F NMR signals from the anesthetic molecules will be used to detect their presence and assess the environments they occupy in brain. Distribution of anesthetic within brain tissue will be studied with ISIS- localized two-dimensional Chemical Shift Imaging. Uptake kinetics will be established in brain. To define the molecular environment of the binding site(s) T2-relaxation times of anesthetic molecules in brain will be measured.

Hemodynamic changes induced by general anesthesia will be visualized using 1H BOLD (Blood Oxygenation Level Dependent) contrast imaging. Analysis of the time sequence of 3D image blocks will be performed by an exploratory unsupervised method to exact functional activity maps. 3D MR angiograms will be recorded to eliminate effects from large veins.

Regional changes in cerebral energy metabolism occurring during anesthesia will be detected and monitored by ISIS-localized 31P 2D-Chemical Shift Imaging which retains chemical shift information. Changes in glutamate, glutamine, gamma-aminobutyric acid and lactic acid levels will be mapped using water-suppressed, ISIS-2D CSI spin-echo 1H spectroscopy.

Data from distribution, functional, and metabolic maps will be correlated with each and with high resolution 1H anatomical images obtained during the study. True baseline values for the processes studied will be established with measurements on awake rabbit brain. Preliminary results from 19F, 31P and 1H MR experiments at 4.7T are presented to demonstrate the feasibility of the proposed project.

R01GM053175

1996-04-01

2002-03-31