? ? There is no in vivo method for mapping the cerebral metabolic rate of oxygen consumption that combines safety with high temporal and spatial resolution, despite the importance of oxygen consumption in neurological disease and functional studies. For example, in the decision to treat ischemic tissue during stroke with potentially dangerous thrombolytic agents, it is not known how much tissue it is possible to save. Threatened, yet potentially viable tissue with restored blood flow maintains some oxygen consumption. Therefore, the ability to measure oxygen consumption in the ischemic area would give clinicians information about how much possible benefit a patient may receive with therapy. Another example of the importance of oxygen consumption is in Alzheimer's Disease (AD), where it is known that oxygen metabolism is hampered due to mitochondrial deficiencies, yet there is no clinically usable method for measuring these changes in AD patients. A technique that measures oxygen consumption could be of diagnostic and prognostic value to patients with dementia, and help track the efficacy of emerging therapies for AD. This proposal is based on a stable, non-toxic, naturally-occurring, and nuclear magnetic resonance (NMR) active form of oxygen: 17O. Because 17O2 gas is NMR invisible and its metabolic product H2170 water is NMR visible, 17O can be used as a non-invasive and non-radioactive metabolic tracer for magnetic resonance imaging (MRI). In the indirect detection method, water containing 17O shortens the local T1Rho and T2 of protons in a concentration dependent manner due to spin-spin coupling. The T1 Rhp based methods allow for decoupling of the 1H-17O interaction that will provide precise local H217O concentrations without artifacts, implemented on existing clinical scanners. In this proposal, a novel precision delivery system for tracer delivery will be developed. By pairing this with emerging magnetic resonance pulse sequences and quantitative in vivo methods for non-invasively measuring the arterial input of the tracer, maps of oxygen metabolism will be generated in a large animal model. Our hope is that the completion of this research will spur clinical trials for 17O imaging of stroke and AD. The public health impact of this research is that it will improve the ability of physicians to make decisions about the diagnosis and treatment of diseases of the nervous system. In particular, new information could be gained to guide the treatment of stroke and Alzheimer's Disease. ? ? ?
| Mellon, Eric A; Beesam, R Shashank; Elliott, Mark A et al. (2010) Mapping of cerebral oxidative metabolism with MRI. Proc Natl Acad Sci U S A 107:11787-92 |
| Mellon, Eric A; Lee, Seung-Cheol; Pickup, Stephen et al. (2009) Detection of lactate with a hadamard slice selected, selective multiple quantum coherence, chemical shift imaging sequence (HDMD-SelMQC-CSI) on a clinical MRI scanner: Application to tumors and muscle ischemia. Magn Reson Med 62:1404-13 |
| Mellon, Eric A; Beesam, R Shashank; Baumgardner, James E et al. (2009) Estimation of the regional cerebral metabolic rate of oxygen consumption with proton detected 17O MRI during precision 17O2 inhalation in swine. J Neurosci Methods 179:29-39 |
