MR MEASUREMENT OF CEREBRAL OXYGEN CONSUMPTION RATE

Measurement of cerebral metabolic rate of oxygen (CMRo2) in response to increased neuronal activity is critical to our understanding of energetics associated with brain function. Many aspects of the hemodynamic and metabolic responses underlying the blood oxygen level dependent (BOLD) fMRI contrast remain poorly understood and controversial. At the heart of this controversy is the effect of elevated neuronal activity on regional cerebral oxygen consumption rate. The few existing methodologies for CMRo2 measurement are widely debated and remain to be experimentally validated. The solution to this problem requires new approaches. The aim of this proposal is to develop a new methodology, based on magnetic resonance imaging and spectroscopy, for quantitative measurement of CMRo2 in rat brain under conditions of basal and elevated neuronal activity at 9.4 Tesla. The technique proposed herein employs an oxygenation-sensitive, biocompatible, 19F- labeled, artificial, blood substitute perfluorocarbon (perflouro- 15-crown-5-ether). The relaxation rate constants of the 19F nuclides on the perfluorocarbon are linearly dependent on the dissolved paramagnetic oxygen concentration and, thus, allow a straightforward measurement of oxygen tension. In conjunction with perfusion measurement using arterial 1H spin-labeling technique, regional cerebral oxygen consumption can be derived. This methodology will be vigorously validated in the well- established hypercapnia model in vivo and ex vitro. The ultimate goal of this proposal is to apply this methodology for CMRo2 measurement in forepaw stimulation in rat. While this proposal focuses on quantifying CMRo2 in brain, the developed technique could be useful for investigation of tissue viability and function in other tissue organs.