Many new noninvasive brain imaging techniques have been developed and proven in both animal and human studies. There is a great need to adapt these methods to perform investigations in children in order to exploit their potential to investigate the neurobiological bases of many childhood disorders. The dynamic nature of the developing brain requires that the brain imaging methods be applicable to studies of normal development. Magnetic resonance methods are well suited to this task. The magnetic resonance center (MRC) at Yale has long standing experience with the development of new magnetic resonance techniques for investigation of brain metabolism and function. Dr. Douglas Rothman, Director of the MRC, and Dr. Graeme Mason will be investigators in the study. Our group has developed magnetic resonance spectroscopic (MRS) methods that focus of measurement of specific neurotransmitter systems. We were the first to measure GABA in the human brain and have combined carbon 13 stable isotopes to measure dynamic changes in glutamate, glutamine and GABA in vivo. All these methods and protocols have been proven in studies in adults. These noninvasive methods must now be adapted to permit investigations in children. There are several modifications of these current protocols that are required to apply these MRS methods successfully to children.
The specific aims of our project are: 1. Determine age-dependent changes in brain oxidative metabolism of glucose using C13 MRS; 2. Determine age-dependent changes in brain glutamate/glutamine cycling. Our new MRC is scheduled to open at the end of this year and the new instrumentation will ensure that the studies are successful. The center will have a new 4 Tesla human MR system that will provide the increased sensitivity to decrease imaging time without sacrificing spatial resolution. The development of this novel noninvasive neuroimaging technique will provide an important tool for further investigations in the study of normal development, alteration of brain neurotransmitter metabolism by drugs, and of the relationship of brain neurotransmitter metabolism to brain function.
| Novotny Jr, Edward J; Fulbright, Robert K; Pearl, Phillip L et al. (2003) Magnetic resonance spectroscopy of neurotransmitters in human brain. Ann Neurol 54 Suppl 6:S25-31 |
