The overall objective of this proposal is to develop a three-dimensional MR imaging protocol to investigate the phosphorus-31 metabolism in the muscle tissue in the lower extremities of diabetic patients. Fifteen million people suffer from diabetes mellitus in the United States and there are 650,000 new cases diagnosed each year. Changes in the structure of the basement membrane of capillaries and neuropathy of the autonomic nerves create an effective ischemia in localized capillary beds in the lower leg and foot. Anatomical methods exist for assessing the blood flow and nerve viability in the lower legs and feet of diabetics. However, these techniques do not provide a direct assessment of the metabolic state of the affected muscle tissue. Phosphorus magnetic resonance spectroscopy (MRS) has been used to study the metabolism of muscle tissue and assess the metabolic state of ischemic tissue in a noninvasive way in humans. The current MRS localization technique that can be used to provide a regional assessment of the lower leg and foot with the ability to identify focal areas of ischemia is chemical shift imaging (CSI). However, a scan of the lower extremities having a resolution that is high enough to identify local areas with poor blood flow using the currently available CSI technique would take more than 21 minutes making the MR examination prohibitively long. We have exploited the recent advances in high-speed magnetic resonance imaging techniques to develop a method for directly creating images of a single phosphorus metabolite (e.g. phosphocreatine) in human skeletal muscle. We have successfully acquired pure phosphocreatine images of human skeletal muscle in normal volunteers having a spatial resolution of 0.23 cm3 in 2 minutes on a whole body MR scanner. We propose to establish a protocol using a 3-dimensional technique for the study of muscle viability in the lower extremities of diabetic patients who suffer from complications resulting from polyneuropathy and localized ischemia.
