Oxygen consumption through oxidative phosphorylation is the dominant pathway for supporting cellular energy demands in aerobic tissues such as the brain and the heart. The close coupling between the oxygen utilization process and the cellular energy demand must exist. The nature of this coupling in the normal tissue and perturbations induced in this coupling under pathological conditions remains a central problem in biomedical research. Ability to image oxygen utilization rates non-Invasively, rapidly, and accurately would be enormously advantageous in efforts aimed at quantifying and understanding this coupling. Particularly, this would be crucial for resolving central questions concerning the role played by oxidative phosphorylation in supporting increased neuronal activity. Specifically, the problem is whether alterations in regional cerebral oxygen consumption rate (CMR02) match the responses of cerebral blood flow (CBF) and/or cerebral glucose consumption rate (CMRgIc) during brain activation. This question is significant not only for understanding the bioenergetics of brain function, but also delineating the mechanisms underlying the functional magnetic resonance imaging (fMRI) technique based on the blood oxygenation level dependent (BOLD) contrast. Although fMRI, introduced about a decade ago, is already the most commonly used tool in contemporary cognitive sciences research, many aspects of its mechanism, and spatial and temporal specificity remain poorly understood. The questions concerning oxygen consumption in the brain persist predominantly because current methods of CMR02 suffer from limitations. In this application we propose to develop and utilize a method based on using 17-0 magnetic resonance spectroscopic (MRS) imaging at very high magnetic fields. We further propose to use this approach for imaging CMR02 in animals and humans non-invasively in order to study the relationships between neuronal activity and CMR02, and to investigate the relationship among CMR02, CBF and BOLD changes under graded neuronal stimulation. Although superficially similar to positron-emission tomography (PET) approach based on 15-0, this method has significant advantages in with respect to acquisition of the necessary data and modeling to calculate CMR02. Extensive preliminary data are presented demonstrating a high signal-to-noise for the 170 MRS imaging measurement at high magnetic fields of 7 to 9.4 Tesla in rats and humans, and that the proposed goals can be achieved.
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