MR DIAGNOSIS OF MUSCLE METABOLISM AND FUNCTION

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The long-term goal is to develop diagnostic procedures for human muscle function using well established strategies previously used for evaluating the metabolic and contractile properties of animal muscle. In this project we use imaging and spectroscopy to define the basis energetic paradigm in normal limb muscle. First, we develop and validate a new exercise stress test to measure oxidative and contractile capacity of human limb muscle. Second, we use these capacities to assess muscle function based on the energy balance attained during normal exercise. Quantitative Energetic Stress Test: This test uses neural stimulation in ischemic muscle to determine ATPase (contractile) capacity as the rate of creatine phosphate breakdown (dPCr/dt). The PCr recovery rate after ischemia defines the ATP synthesis (oxidative) capacity (Specific Aims 1 and 2). Together these capacities yield quantitative information beyond muscle fiber-type classification for assessment of muscle functional capacity. Energy Balance: To validate the predictive power of the strategy, we determine the energy balance attained under steady-state neural stimulation and natural exercise. We test whether a higher oxidative capacity results in 1) less depletion of PCr at the same exercise level and 2) greater sustained force production and exercise levels. This work builds on an extensive body of spectroscopic information gained from normal and diseased human muscle, and on principles of bioenergetics and metabolic integration derived from animal studies. What is new is the energy balance concept is applied for the first time to human muscle in a way in which both the supply and demand side of the metabolic economy can be quantitatively assessed and related to muscle functional capacity.