A normal oxidative capacity of peripheral tissues requires adequate capabilities for oxygen delivery and use. In diabetes mellitus, there are impairments to vascular structure and function that limit oxygen delivery to peripheral tissues. In addition, there are reductions in skeletal muscle fiber size and the activity of oxidative enzymes that reduce the capacity for oxygen use. As a result, there are exaggerated changes in phosphorus metabolites and pH in exercising diabetic muscle, reducing fatigue resistance and enhancing glycogenolytic flux. The development of a non-invasive method for quantifying oxygen delivery and use impairments in diabetic skeletal muscle and evaluating their functional consequences would increase our understanding of this disease. The overall objective of the proposed studies is therefore to develop a novel method for quantifying oxygen consumption in skeletal muscle by magnetic resonance imaging (MRI) and to integrate it with measurements of mechanical function and skeletal muscle biochemistry.
The first aim i s to develop an MRI method for absolute quantification of the rate of oxygen consumption (VOw) in skeletal muscle. We will make these measurements by first implementing and validating MRI methods for quantification of perfusion and then by developing and validating a novel method for mapping blood oxygen content. Combining these measurements through the Fick equation will allow us to form calculated VO2 maps of exercising muscle.
The second aim i s to develop methods for regional, integrated studies of oxygen consumption, cellular energetics, and force production. We will do so first by interleaving non-localized, but highly temporally resolved, 31p MR spectra with VO2 image acquisitions. In other studies, we will use interleaved acquisitions of 3,p MR spectroscopic images and VOemaps to obtain highly spatially resolved metabolic information in the exercise steady state. Overall, these studies will provide an important new tool for evaluating oxidative metabolism and provide novel information about the effects of oxidative metabolism impaimlents in skeletal muscle metabolism and function in vivo. Moreover, these techniques will be suitable for future studies of the effects of exercise training or other interventions in diabetic animal models.
