Despite the high occurrence of muscle dysfunction and its dramatic effect on performance in daily ambulatory activities, little is known about the mechanisms involved in the restoration of muscle function. Rehabilitation of muscle function has mainly relied on empirical evidence. Therefore the overall goal of this proposal is to elucidate the physiological mechanism underlying the restoration of muscle function and functional performance. The investigators hypothesize that improvements in muscle function and functional performance during rehabilitation are directly related to alterations in the in vivo metabolic properties and gross morphology of skeletal muscle. For this purpose, 30 patients who underwent 5-10 weeks of cast immobilization following ankle surgery will be subjected to a 10 week rehabilitation program. During the course of rehabilitation 31P-Magnetic Resonance Spectroscopy (MRS), Magnetic Resonance Imaging (MRI), muscle biopsy, muscle function and functional performance tests will be performed. Innovative localized 31P-MRS measurements will be implemented to measure changes in the muscle's in vivo ability to supply energy via aerobic and anaerobic means as well as its ability to manage energy during contraction. In addition, 3- dimensional MRI procedures will be used to quantify the changes in maximal muscle cross-sectional area and total muscle volume during the course of rehabilitation. Changes in these in vivo measures of energy supply, energy demand and muscle morphology will be related to changes in standard in vitro measures. Ultimately, changes in the in vivo measures of muscle energetics and muscle morphology during the course of rehabilitation will be related to improvements in muscle function and functional performance. Muscular endurance, power and strength will be characterized by standard isometric and isokinetic tests, whereas the performance in daily ambulatory activities will be evaluated via simple tasks such as stair climbing, walking and one legged toe raises. The investigators anticipate that the combined use of basic and applied measures of skeletal muscle during the course of rehabilitation, as proposed in this study, will help to elucidate the physiological mechanisms underlying the restoration of muscle function. In addition, they anticipate that this study will provide essential feedback for the design and development of more specific rehabilitation interventions which focus on the underlying pathophysiology, providing a faster reintegration into the community.
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